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COPYRIGHT DEPOSIT. 



Plate 













I. 
PALE YELLOW. 












II. 
LIGHT YELLOW, 












III. 
YELLOW. 












IV. 

REDDISH YELLOW. 












Y. 

YELLOWISH RED. 












VI. 

RED. 












1 BROWNISH RED. 






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VIII. 

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1 


I 



Scale of Urinary Colors, according to Vogel. 



Clinical 
Examination of the Urine 

AND 

Urinary Diagnosis 

A Clinical Guide for the Use of Practitioners and 
Students of Medicine and Surgery 



J. BERGEN OGDEN, M.D. 



NEW YORK, N, Y. 

LATE INSTRUCTOR IN CHEMISTRY, HARVARD UNIVERSITY MEDICAL SCHOOL ; ASSISTANT 
CLINICAL PATHOLOGY, BOSTON CITY HOSPITAL ; MEDICAL CHEMIST TO THE CARNEY 
HOSPITAL ; VISITING CHEMIST TO THE LONG ISLAND HOSPITAL, BOSTON. 



ILLUSTRATED 



Second Bbttion, Uborou^bl^ IRevise^ 



PHILADELPHIA, NEW YORK, LONDON 

W. B. SAUNDERS & COMPANY 
1903 



' J ' i.^ 11 *» *j 




THE LIBRARY OF 
CONGRESS. 

Two Copies Receive* 

AUG 20 1903 

Copyright fcntfy 
CUS§ c^ XXc. N« 

l^ I. ^ '^ L 

COPY 8. 



Copyrighted and printed, 1900, by W. B. Saunders & Co. 
Reprinted September, 1901. Revised, copyrighted, and 
printed. May, 1 903. 



Copyright, 1903, by W. B. Saunders & Company. 



PRESS OF 
W. B. SAUNDERS & COMPANY. 



TO 



JBDwarD Sticftneis MooD, B»/IR„ /IR.2)», 

PROFESSOR OF CHEMISTRY, HARVARD UNIVERSITY MEDICAL SCHOOL* 

AS A SLIGHT TOKEN OF HIGHEST ESTEEM AS 

A TEACHER AND FRIEND, 

THIS VOLUME 

IS RESPECTFULLY DEDICATED BY 



THE AUTHOR. 



PREFACE TO THE SECOND EDITION 



In revising this work for the second edition a special 
■effort has been directed toward making the text complete 
and bringing it thoroughly up to date. Such typographi- 
cal errors as have come to my notice have been corrected. 
Important changes have been made in Part I, especially 
in connection with the determinations of Urea, Uric Acid, 
and Total Nitrogen ; and the subjects of Cryoscopy and 
79-Oxybut}^ric Acid have been given a place. Only minor 
changes have been made in Part II. 

I am indebted to those who reviewed the first edition of 
the work for their suggestions, many of which have been 
adopted, and for their kind words of approval. 

J. B. O. 

262 Fifth Ave., New York City. 



PREFACE 



The design of this work is to present in as concise a 
manner as possible the chemistry of the urine and its rela- 
tion to physiologic processes ; the most approved working 
methods, both qualitative and quantitative ; the diagnosis 
of diseases and disturbances of the kidneys and urinary 
passages. 

Since most of the books on the urine at the present time 
are devoted almost exclusively to urinary chemistry, and 
since a knowledge of urinary diagnosis is obtainable only 
by an extended search through various works on medicine, 
surgery, pathology, and chemistry, I have long felt the need 
of a treatise which takes up in detail the subject of urinary 
diagnosis and the application of information furnished by 
careful chemic and microscopic examination of the urine. 

The work naturally falls into two parts. 

In Part I chemic and microscopic methods are described 
in detail, and numerous illustrations, many of which are 
original, have been introduced, thus enabling the student 
and practitioner who has not had special training in urinary 
analysis to obtain accurate results. 

In Part II special attention has been paid to diagnosis, 
which includes our present knowledge of the character of 
the urine, the diagnosis and differential diagnosis of dis- 
turbances and diseases of the kidneys and urinary passages, 
whether they be local or general, medical or surgical ; a 
brief enumeration of the prominent clinical symptoms of 
each disease ; and, finally, the peculiarities of the urine in 
certain general diseases of the body. 

My chief object, therefore, in presenting this work is to 
furnish the student and practitioner with a more complete 
clinical guide to urinary diagnosis than I have heretofore 
met with in a single volume. 

No attempt has been made to incorporate in this volume 
more than a limited number of references to the literature 

9 



10 PREFACE. 

on the various urinary subjects that have been considered. 
Those references given are, for the most part, to subjects 
that are still under discussion, or to those that are com- 
paratively new to medical literature. 

Numerous books and original monographs have been 
■consulted, and the views of standard authorities have been 
freely quoted in this work. I have endeavored in all cases 
to give full credit to the various writers throughout the text. 
If in any instances I have been remiss, I take this oppor- 
tunity of thanking those who have unwittingly aided me by 
their researches and writings. 

In conclusion, I wish to express my sincerest thanks to 
Dr. Edward S. Wood for the many valuable suggestions 
Jie has given me in the production of this volume. 

J. Bergen Ogden. 



CONTENTS 



PAGE 

Introduction 17 

CHAPTER I. 

Constituents of Normal Urine 21 

Physical Properties of Urine 24 

CHAPTER n. 

Organic Constituents of Normal Urine 41 

Urea . 41 

Table of Approximate Proportions of Urea in Urine, for Clinical 

Use 55 

Uric Acid . . . . 59 

Xanthin Bases 72 

Nucleic Acid 76 

Allantoin 77 

Kreatin and Kreatinin 79 

The Aromatic Substances in Urine 81 

Urinary Coloring- matters 91 

Other Organic Constituents of the Urine 97 

CHAPTER III. 

Inorganic Constituents of Normal Urine 100 

Chlorides 100 

Phosphates 107 

Sulphates * . . . . 112 

Carbonates 116 

Iron 117 

Hydrogen Peroxide I17 

Urinary Cryoscopy 118 

CHAPTER IV. 

Abnormal Constituents of Urine 119 

Proteids 119 

Albumin I20 

Globulin 135 

Albumoses 136 

Peptone I39 

Method of Separation and Identification of Proteids 141 

Nucleo-albumin ; . . . 142 

Hemoglobin 144 

Fibrin 145 

CHAPTER V. 

Carbohydrates 147 

Glucose 147 

Lactose . 166 

Levulose 167 

Laiose 1 68 

11 



12 CONTENTS. 

PAGE 

Substances Allied to Sugar 169 

Inosite 169 

Glycuronic Acid 171 

Cane Sugar 172 

Pentoses 173 

Acetone 173 

Diacetic Acid . 176 

Oxybutyric Acid 178 

Bile 179 

Biliary Acids 182 

Ehrlich's Diazo Reaction = 186 

Various Metallic and Nonmetallic Substances 188 

Hematoporphyrin . . . , 191 

Melanin 194 

Ptomaines and Leucomaines. — Toxicity of Urine 196 

CHAPTER VI. 

Urinary Sediments 201 

Methods of Obtaining Urinary Sediments 202 

The Preparation of Sediments for Microscopic Examination . . . 208 

Urinary Sediments 209 

Nonorganized Sediments , 210 

Organized Sediments 232 

Extraneous Substances Found in Urine . . , 263 

Preservation of Urinary Sediments 263 

Micro-organisms 265 

Parasites . 269 

CHAPTER VII. 

Urinary Concretions « 272 



PART n. 

Diagnosis . 284 

CHAPTER VIII. 

Disturbances and Diseases of the Kidneys 284 

Active Hyperemia 284 

Passive Hyperemia 291 

Acute Diffuse Nephritis 294 

Subacute Glomerular Nephritis 302 

Chronic Interstitial Nephritis 307 

Senile Interstitial Nephritis . , 315 

Chronic Diffuse Nephritis 316 

Amyloid Infiltration 319 

CHAPTER IX. 

Diseases of the Kidneys (Continued) 323 

Tuberculosis of the Kidneys 323 

Renal Calculus 326 

Abscess of the Kidney ' . , 328 

Renal Embolism , 329 

Tumors of the Kidney 330 

Cystic Disease of the Kidneys 331 



CONTENTS. 13 
CHAPTER X. 

PAGE 

DlSE.\SES OF THE URINARY TRACT BELOW THE KiDNEY PROPER . 333 

Pyelitis 333 

Acute Pyelitis 333 

Chronic Pyelitis 335 

Calculous Pyelitis 337 

Hydronephrosis 339 

Pyonephrosis . 34^ 

Ureteritis 343 

Cystitis 344 

Acute Cystitis 344 

Chronic Cystitis 34^ 

Tuberculosis of the Bladder 34^ 

Tumors of the Bladder 35^ 

Prostatitis 353 

Acute Prostatitis 353 

Prostatic Abscess 355 

Chronic Prostatitis 355 

Tubercular Prostatitis 35^ 

Cancer of the Prostate 359 

Urethritis 359 

Chyluria 362 

Hemoglobinuria 3^4 

Pneumaturia 366 

Uremia 367 

Diabetes Mellitus 370 

Diabetic Coma . 375 

Diabetes Insipidus 377 

CHAPTER XI. 

The Urine in Diseases outside of the Urinary Tract .... 380 

Fever Urine 380 

Urine of Chronic Disease (not Renal) 381 

Typhoid Fever 382 

Yellow Fever 383 

Typhus Fever 384 

Relapsing Fever 384 

Pneumonia 385 

Pulmonary Tuberculosis 386 

Malarial Fever 387 

Erysipelas 388 

Cholera 389 

Scarlet Fever 390 

Diphtheria 392 

Smallpox 392 

Acute General Peritonitis 393 

Intestinal Obstruction 393 

Acute Yellow Atrophy of the Liver 394 

Hysteria 395 

Cerebrospinal Meningitis 395 

Melancholia 396 

Acute Myelitis 396 

Epilepsy 397 

Acute Articular Rheumatism 397 

Gout 398 

Anemia 399 

Scurvy 399 



14 CONTENTS. 

PAGE 

Carbolic Acid Poisoning 400 

Poisoning by Phosphorus and Arseniureted Hydrogen 400 



APPENDIX A. 

Method of Recording Urinary Examinations 402 

Order of Applying Tests 405 

• jSIethod of ]Making Diagnoses of Diseases of the Kidneys from the 

Urine 405 



APPENDIX B. 

rka.gents and apparatus for qualitative and quantitative 

Analysis of Urine 408 

Liquid Reagents 408 

Solid Reagents 409 

Apparatus 409 

INDEX 411 



CLINICAL 

EXAMINATION OF THE URINE 

AND 

URINARY DIAGNOSIS. 



URINARY ANALYSIS. 



INTRODUCTION. 

The urine is an aqueous solution of organic and inor- 
ganic substances excreted and secreted by glands called 
the kidneys. Assuming that the reader is acquainted with 
the gross and minute structure of the kidneys, it remains 
for us to consider some of the physiologic processes which 
are concerned in the production of the urine. The very 
close relation that exists between the blood-vessels and 
the uriniferous tubules suggests at once the fact that the 
fluid called urine is the product of nature's effort to re- 
move from the body, by way of the blood, those substances 
Avhich are no longer useful to the tissues of the body ; in 
other words, the urine is essentially a solution of waste- 
products of the body. 

Having carefully studied the minute structure of the 
kidneys, we find that, unlike other secreting organs, they 
consist of two parts, so distinct in structure that it seems 
almost impossible to resist the conclusion that their func- 
tions are different, and that the mechanism by which the 
urine is secreted is of a double kind. The uriniferous 
tubules, on the one hand, with their characteristic epithe- 
lium, appear to be merely secreting structures ; while, on 
the other hand, the Malpighian capsules with their glom- 
eruli are structures with insignificant epithelium, strongly 
suggesting that their function is rather one of the nature of 
a filter than of a secreting structure. Such is the theory 
of Bowman, since he first pointed out that certain constit- 
uents of the urine only are put forth by the uriniferous 
tubules, which act in a manner similar to other secreting 
glands, and that the other constituents, including water 
and various soluble and diffusible salts from the blood, are 
apparently filtered out by the glomeruli. It is very evident 
from the vascular arrangement in the kidney that the 

2 17 



18 INTRODUCTION. 

capacity of the kidney for work is closely dependent on the 
flow of blood through it, and this appears to be controlled 
largely by the vasomotor and vasodilator nerves, which are 
supplied by the anterior roots of the eleventh, twelfth, and 
thirteenth dorsal nerves. 

The theory of Ludwig, based on the varying degrees of 
blood pressure in the glomeruli, and the elimination of cer- 
tain constituents of the blood by diffusion or osmosis, can 
hardly be considered tenable in the light of recent physi- 
ologic research. In this theory Ludwig did not consider 
the importance of the renal epithelium in the secretion oi 
urine, as has been well demonstrated by the experiments 
of Heidenhain, who found that by injecting a solution of 
sodium indigo-sulphate into the blood of an animal not 
only the urine became blue, but the epithelial cells lining 
the convoluted tubules and the looped tubes of Henle 
were also colored blue, while there was not the slightest 
trace of blue in the Malpighian bodies. By first dividing 
the spinal cord of an animal and then injecting the indigo 
solution, he also demonstrated the fact that the renal 
epithelium has distinct eliminative power. He found the 
following : That no urine reached the bladder, and the epi- 
thelium lining the convoluted tubules as well as those of 
Henle was stained blue the same as before ; that when the 
animal was killed, a sufficient period after the injection, the 
epithelium was found to be free from coloring-matter, and 
the indigo compound had passed into the lumen of the 
tubules, where, in the absence of water from the glomeruli, 
it had cr}'Stallized. It often happens in some diseases of 
the kidneys in which the renal tubules become stripped of 
their epithelium that the urea and other products of the 
metabolism are no longer so thoroughly removed from the 
body, but remain in the blood, and frequently cause the 
symptom known as uremia, often when the watery constit- 
uent is eliminated in abundance. 

It is, therefore, fair to conclude that the renal epithelial 
cells are normally actively engaged in the process of secre- 
tion, and that the water and some of the soluble salts of 
the urine are secreted largely by the glomeruli, the func- 
tion of which is regulated chiefly by the varying degrees 
of blood pressure. 

Too much can not be said regarding the importance of 
an accurate examination of the urine, — both chemic and 



INTRODUCTION. 19 

microscopic, — for it is by this means only that the condi- 
tion of the kidneys — whether healthy or diseased^ — and 
their capability for work can be definitely determined. 
Furthermore, by the correct interpretation of the results of 
modern methods of urinary analysis, the variations in the 
body metabolism — nutrition and waste — can also be deter- 
mined, and such information is often of the greatest impor- 
tance to the physician in judging of the diagnosis and 
prognosis of disease. While it is impossible to diagnosti- 
cate all diseases from an examination of the urine, it is, 
nevertheless, a fact that an extensive disease, whether in 
the kidneys or not, can not exist in the human organism 
without showing its effect in the urine. This is more espe- 
cially true in connection with diseases and disturbances of 
the kidneys, when any deviation in the urine from the nor- 
mal furnishes us with the only reliable data concerning the 
nature of the diseased process. 

It is, therefore, essential that the practitioner and student 
of medicine should become perfectly familiar with those 
features of the urine that are characteristic of certain dis- 
eased conditions ; and also to become acquainted with 
those alterations of the urine found in various functional 
disturbances of the body, such as derangements of gastric 
and intestinal digestion, etc. 

Nomenclature. — The student of medicine is frequently 
confused by the complicated nomenclature of the diseases 
of the kidneys. He finds that the various diseased condi- 
tions of these organs have received a variety of names, and 
that the terms employed indicate a number of pathologic 
conditions. This is partly due to the fact that a given 
cause does not always produce the same anatomic lesions 
in the kidneys, and partly to the fact that a marked lack of 
uniformity exists between the terms used by the pathologist 
and those used by the clinician in the description of any 
given kidney disease. What is certainly needed are more 
numerous and more thorough clinical observations, and, 
in every instance possible, a careful study of these observa- 
tions in connection with the pathologic findings. 

As Councilman ^ has said : '' For the present, the classi- 
fication of the diffiise lesions of the kidney must be founded 
on the character of the anatomical lesions. A classification 

^ "American Journal of the Medical Sciences," July, 1897. 



20 INTRODUCTION. 

on an etiological basis is the most scientific and the simplest, 
but we know little or nothing of the etiology of these dis- 
eases. Various forms of disease in other organs, partic- 
ularly of the heart, are often found associated with them. 
Bacteriological investigation has shown in many cases the 
presence of certain organisms in the kidney. In most 
cases the bacteria are found in some other lesions and in 
the blood, and their presence in the kidney is but a part of 
a general septicemia. Moreover, the same condition in 
the kidney may be associated with a variety of organisms, 
and the same organism may be associated with widely dif- 
ferent anatomical lesions." 

The nomenclature which the author has adopted in this 
work is calculated to be abreast with recent pathologic 
investigation. The term chronic parenchymatous nephritis^ 
which was introduced by Virchow (1852), has been re- 
placed by the term subacute glomerular nephritis. This 
change is based upon the fact that the lesion which was 
formerly thought to be confined to the epithelial constit- 
uents of the kidney has recently been found to involve 
chiefly the glomeruli ; also because the disease is sub- 
acute rather than chronic in duration. 

In the use of the word nephritis it must be understood 
that the lesions referred to are not necessarily inflamma- 
tory ; while inflammatory exudation in some form is fre- 
quently present, it is safe to say that the majority of lesions 
of the kidneys are not inflammatory. 

We shall frequently refer to diffuse lesions of the kidney, 
such as acute diffuse nephritis and chronic diffuse nephri- 
tis. By the term diffuse we do not mean that all parts of 
the kidney are equally affected. It has been demonstrated, 
by the study of degenerations and the effect of poisons, 
that in some instances the most marked changes are in the 
convoluted tubules, while in others they are in the loops 
of Henle or in the collecting tubules. All parts of the 
kidney are equally exposed to the action of chemic irri- 
tants, but all may not be equally susceptible. Likewise, in 
glomerular lesions of the kidney the accompanying degen- 
erative lesions in the renal epithelium may be in part or 
wholly secondary to the lesions of the glomeruli. In other 
words, in diffuse lesions of the kidney various parts of the 
organ may be primarily or secondarily affected, but usually 
not all parts are affected to the same extent. 



CHAPTER I. 

CONSTITUENTS OF NORMAL URINE. 

The complexity of the urine ehminated under normal 
conditions is well shown by the following classification of 
Hoppe-Seyler : 

1. Urea and allied substances : Uric acid, allantoin, 
oxalic acid, xanthin, guanin, kreatinin, and thio- (sulpho-) 
cyanic acid. 

2. Fatty and other nonnitrogenous substances : Fatty 
acids of the series C,iH2n02 ; oxalic, lactic, glycerophos- 
phoric acids ; minute quantities of certain carbohydrates (?). 

3. Aromatic substances : The ethereal sulphates of phe- 
nol, kresol, pyrocatechin, indoxyl, and skatoxyl ; hippuric 
acid ; aromatic oxyacids. 

4. Other organic substances : Pigments ; ferments, espe- 
cially pepsin ; mucous and humous substances ; kynurenic 
acid. 

5. Inorganic salts : Chlorides of sodium and potassium ; 
potassium sulphate ; sodium, calcium, and magnesium 
phosphates ; silicic acid ; ammonia compounds, and cal- 
cium carbonate. 

6. Gases : Nitrogen and carbonic acid. 

Quantitative Composition of Normal Urine. — A num- 
ber of estimations of the constituents of normal urine have 
been made, but the following table by Parkes gives the 
most accurate determination thus far known : 

AMOUNTS OF URINARY CONSTITUENTS ELIMINATED IN 
TWENTY-FOUR HOURS (PARKES). 

By an Average Man Weigh- Per Kilogram of 
Constituents. ing Sixty-six Kilograms. Body-weight. 

"Water 1500.00 grams. 23.000 grams. 

Total solids 72.00 " i.ioo " 

Urea 33-'^^ *' 0.500 " 

Uric acid 0.55 " 0.008 " 

Hippuric acid 0.40 " 0.006 " 

21 



22 CONSTITUENTS OF NORMAL URINE. 

AMOUNTS OF URINARY CONSTITUENTS ELIMINATED IN 
TWENTY- FOUR HOURS {TARKES). — {Con^mued.) 

By an Average Man Weigh- Per Kilogram of 
Constituents. ing Sixty-six Kilograms. Body-weight. 

Creatinin 0.91 grams. 0.014 grams. 

Pigment and other organic sub- 
stances . . . . , 10.00 " o. 151 " 

Sulphuric acid 2.01 " 0.030 " 

Phosphoric acid . ... ... 3.16 " 0.048 " 

Chlorine 7-8.00 " 0.126 " 

Ammonia o. 77 '* . . 

Potassium 2.50 " . . 

Sodium 11.09 " • • 

Calcium o. 26 *' . . 

Magnesium 0.21 " . . 

Yvon and Berlioz ^ have carefully studied the urines of 
both male and female, and have constructed the following 
comparative table, which includes the amounts of some of 
the more important urinary solids, excepting chlorides : 

Male. Female. 

Quantity (per diem) 1360 c.c. iioo c.c. 

Specific gravity 1022 grams 102 1 grams 

Urea (per liter) 21.5 " 19.0 " 

*' (per diem) 25.6 " 20.5 '* 

Uric acid (per liter) 0.5 " 0.55 " 

" " (per diem) 0.6 " 0.57 " 

Phosphoric acid (per liter) 2.5 '* 2.4 " 

" *' (per diem) 3.2 " 2.6 " 

Collection of Urine for Analysis. — The whole quantity 
of urine for twenty -four hours should, in all cases, be col- 
lected, thoroughly mixed, and carefully measured. If the 
entire secretion for twenty-four hours can not be conven- 
iently submitted for analysis, a sample (from four to eight 
ounces) of the mixed urine, together with a statement of the 
quantity eliminated in twenty-four hours, will suffice. 

A four or five pint bottle, peifectly clean, is perhaps the 
most convenient receptacle for the urine during its collec- 
tion. The bottle should be well corked after each addition 
of the urine, and should stand in a cool place. The urine 
should never be collected or allowed to stand in an open 
or, above all, in an unclean vessel. Every effort should be 
made to avoid the introduction of particles of dust, fecal 
matter, expectorated matter, and the like, all of which seri- 
ously interfere with the subsequent analysis of the urine. 

1 "Lancet," vol. II, 1888, p. 629. 



COLLECTION OF URINE. 23 

It should be borne in mind that the urine begins to un- 
dergo the process of decomposition within a few hours after 
it has been voided, although the changes are usually very 
slight and unimportant, providing the urine is kept cool. 
In order, however, to guard against decomposition of the 
urine during its collection, it is advisable to put into the 
bottle one ounce of a cold saturated aqueous solution of boric 
acid (about four per cent.), or two or three drops of formalin 
(not more^); stopper tightly, and then add the urine imme- 
diately after each micturition. The ounce of boric acid 
solution is to be deducted from the total quantity of urine 
when it is measured. 

A convenient time to begin to save the urine is at 7 a. m. 
At that hour, or such other time as may be decided upon, 
the bladder should be emptied, and the urine thrown away ; 
then all the urine voided in the subsequent twenty-four 
hours, including the amount of urine in the bladder at 7 
A. M. the next day, will represent the total quantity for 
twenty -four hours. It is often important to collect the day 
and night urine separately ; in such cases the urine voided 
between 7 a. m. and 7 p. m. is to be placed in one bottle, 
and that voided between 7 p. m. and 7 a. m. in another 
bottle, carefully labeling each. 

For the qualitative examination a single specimen of 
urine, the product of one micturition, may be collected. 
Since there is a marked variation in the urine at different 
times of day, a specimen should be taken at a time when 
the urine is most likely to contain the largest proportion 
of morbid elements — i. e., about midday or between three 
and four hours after a meal. For the purpose of compari- 
son such a sample should, however, always be accom- 
panied by another specimen collected in the morning on 
rising — i. e., at a time when the urine contains the smallest 
proportion of abnormal elements. As previously indicated, 
the urine should always be poured into a perfectly clean 
bottle, and should be submitted for examination in a per- 
fectly fresh condition, — that is, before decomposition has 
begun, — since the morphologic elements, such as casts, 
epithelium, etc., in a urine that has decomposed may dissolve 
or become so altered that they are beyond recognition. 

1 When more than two or three drops of formalin are added to from one 
pint to one quart of urine, a pecuhar crystalUne (?) precipitate is apt to be 
thrown down ; this compound is supposed to consist of formalin and urea. 



24 CONSTITUENTS OF NORMAL URINE. 

PHYSICAL PROPERTIES OF THE URINE. 

Quantity. — For a healthy adult the average quantity of 
urine in twenty -four hours is 1500 c.c, or about 50 fluid- 
ounces. The normal variation is between 1 200 and 1600 
c.c, according to the size, habits, and sex of the individ- 
ual — for example, a female of average size usually passes 
less urine in twenty-hours than an averaged-size male. 
Furthermore, a small adult, male or female, may not elimi- 
nate more than 1200 c.c, and yet be in a state of perfect 
health. The habits of the person have, perhaps, the 
greatest influence on the twenty-four-hour quantity in 
health ; the habitual ingestion of considerable quantities of 
liquids, liberal eating, and the like, may cause the quantity 
to reach 1600 c.c, or even more. On the other hand, 
exercise, free perspiration, the ingestion of very little liquid, 
may result in the elimination of a small quantity of urine, 
even below 1200 c.c. 

The quantity of urine in health varies considerably with 
the time of day, the largest amount being passed in the 
afternoon, the least at night, and the mean quantity in the 
forenoon. 

The total quantity of urine for twenty-four hours should 
be accurately measured in every case in which the urine is 
to be examined, and it is frequently necessary, particularly 
in disease of the kidneys, to measure the urine every day 
for a period of one, two, or three weeks, in order to ascer- 
tain the average daily quantity. Upon the total quantity 
depend all quantitative determinations, and, therefore, intelli- 
gent inferences as to the capability of the kidneys for work. 

Diminished Quantity. — A diminished quantity of urine 
in twenty -four hours — that is, less than 1500 cc — has the 
following causes : (i) Small quantity of liquid taken ; (2) 
free perspiration ; (3) fever ; (4) diarrhea ; (5) vomiting, and 
the following renal disturbances and diseases : (6) most 
cases of active hyperemia ; (7) passive hyperemia ; (8) first 
and second stages of acute diffuse nephritis ; (9) subacute 
glomerular nephritis ; (10) toward death in all diseases. 

Increased Quantity. — The causes of an increased quan- 
tity of urine in twenty -four hours are as follows: (i) 
Large quantity of liquid taken; (2) diuretic treatment ; 
(3) nervous excitement and some diseases of the nervous 
system (frequently in hysteria, and temporarily in cerebral 



COLOR OF URINE. 25 

hemorrhage) ; (4) diabetes melHtus ; (5) diabetes insipidus ; 
(6) convalescence from acute diseases in general, and the 
following disturbances and diseases of the kidneys : (7) 
convalescence from a severe active hyperemia ; (8) con- 
valescence from an acute diffuse nephritis ; (9) chronic inter- 
stitial nephritis ; (lo) chronic diffuse nephritis ; (i i) amyloid 
infiltration. 

Oliguria is the term applied to those cases in which the 
quantity of urine is very small, typically seen during the 
acute stage of an acute disease, also in those chronic dis- 
eases that are attended with extensive dropsy. 

Anuria is applied to cases in which there is no urine, or 
when only an exceedingly small quantity is passed — in 
other words, complete, or almost complete, suppression of 
wine. This condition is most commonly seen shortly be- 
fore death, particularly in extensive disease of the kidneys. 
Total, or nearly total, suppression may last several days — 
from five to ten. 

Polyuria is a term signifying the excretion of a large 
quantity of urine without any reference to the quantity of 
total solids in twenty-four hours. Hydruria is a term 
signifying the excretion of a large amount of urine — in other 
words, a polyuria — with either a normal quantity or a 
diminution in the total solids for twenty-four hours : for 
example, in marked cases of chronic interstitial nephritis, 
the solids are notably diminished. 

Obstructive suppression occurs when there is a partial 
or complete obstruction to the outflow of urine through 
the ureters, and is sometimes found to be due to the pres- 
ence of impacted calculi in both ureters ; also to the pres- 
sure of a new growth, and occasionally by valves or twists 
of the ureters. In a case reported by Farlow^ obstruction 
was caused by a new growth of the uterine appendages, 
and almost complete obstruction lasted for twelve days. 

Retention of urine is the result of an obstruction to the 
ou^tflow of urine through the urethra, as by a tight urethral 
stricture, the presence of a calculus in the urethra, or by 
some mechanical obstruction in the region of the neck of 
the bladder. 

Color. — I. The color of the urine under normal 
conditions is straw or amber yellow. This, however, 

^ J. W. Farlow, "Boston Medical and Surgical Journal," cxx, p. 333. 



26 CONSTITUENTS OF NORMAL URINE. 

varies considerably even within the range of perfect health. 
The color may be said to vary with the dilution or concen- 
tration of the urine. Thus, a very dilute urine has a pale 
color and may be almost colorless, containing a relatively 
small amount of coloring-matter, and in health is usually 
the result of copious drinking. On the other hand, a con- 
centrated urine usually has a higJi color, contains a relative 
excess of the normal coloring-matter, and is seen w^hen too 
little water is taken, also after free perspiration and vigor- 
ous exercise. It is evident, therefore, that in health the 
color may range from a very pale or watery color through 
the yellows to a high or deep red. For practical purposes 
the color may be termed pale^ normal, and high, according 
to circumstances. 

Vogel has constructed a scale of colors of the urine from 
nature. (See Frontispiece.) These colors are expressed 
as (i) pale yellow; (2) light yellow; (3) yellow; (4) 
reddish-yellow ; (5) yellowish-red ; (6) red ; (7) brownish- 
red ; (8) reddish-brown ; (9) brownish-black. Vogel classi- 
fies these colors into groups of three ; the first three being 
yellow, the second three being red, and the last three 
brown or black. In applying the chart the urine should 
first be filtered if not already perfectly transparent. It 
should then be poured into a glass vessel at least three or 
four inches in diameter, and examined by transmitted light. 
This color chart is of considerable value as a means for 
comparison. 

2. (a) Under pathologic conditions there is a greater 
variation than in health, the color being due either to an 
increase or diminution of the normal pigments, or to the 
addition of one or more pathologic coloring-matters. Very 
pale urines are usually attended with an increased quan- 
tity of urine, as in chronic interstitial nephritis, chronic dif- 
fuse nephritis, amyloid infiltration, well-advanced convales- 
cence from acute nephritis, diabetes mellitus, and diabetes 
insipidus. On the contrary, the urine may have a pale 
color with a diminisJied quantity of urine, as in the inactive 
stage of subacute glomerular nephritis, and in certain 
chronic affections elsewhere in the body, particularly those 
accompanied by marked diminution in the normal solids in 
the urine. 

The urine may have a normal color in certain pathologic 
conditions, particularly in active hyperemia of the kidneys,. 



COLOR OF URINE. 27 

frequently in the early stage of chronic interstitial nephritis, 
and rarely in subacute glomerular nephritis. Occasion- 
ally, in diabetes mellitus when the quantity of urine is in- 
creased to three or four liters, the color is normal, the 
result of an absolute increase of the coloring-matters. 

Urines having a higli color are almost invariably seen in 
the early stage of acute disease, also usually in active and 
passive hyperemia of the kidneys, active stage of subacute 
glomerular nephritis, and in certain diseases elsewhere in 
the body, notably liver diseases, acute articular rheumatism, 
and frequently in cases of chronic rheumatism and chronic 
gout. 

From the foregoing it is seen that, either in health or 
disease, the urine may be pale, normal, or Jiighly colored ; 
consequently, as far as the color alone is concerned, only 
negative inferences can be deduced concerning the existing 
pathologic condition. 

it)) A dark or smoky urine should always be recog- 
nized, for it invariably indicates the presence of an ab- 
normal pigment. Great care should be taken not to 
confound a dark color with a high color. This abnormal 
pigment is most commonly found to be decomposed blood 
pigment (methemoglobin or hematin), although it is fre- 
quently seen after carbolic acid has been taken, and occa- 
sionally after its use as an external application. It is also 
occasionally seen after the use of phenol compounds, 
especially certain drugs, such as salol (when taken in large 
doses), guaiacol, etc. A urine after the ingestion of phenol 
is usually normal in color when passed, but on standing 
exposed to the air soon becomes dark, and may, if allowed 
to stand a still longer time, become almost black — the 
result of the decomposition product of the phenol (hydro- 
chinone). A urine containing bile pigment in the form of 
bilirubin often has a dark color ; when such a urine is 
shaken, the foam will be found to have a decided yellow or 
greenish-yellow color, and as the urine stands exposed to 
the air, it soon takes on a greenish, and if much bile is 
present a marked green, color. The presence in the urine 
of an abnormal pigment called melanin may cause a dark 
urine ; the freshly passed urine usually has a normal color, 
but on standing exposed to the air it gradually grows 
darker from above downward, due to the slow oxidation of 
the chromogen, — melanogen, — which results in the pigment 



28 CONSTITUENTS OF NORMAL URINE. 

melanin. Alkapton,'^ which has a strong affinity for oxygen, 
produces a dark-colored urine. The urine is usually normal, 
or high in color, when passed, but on standing exposed to 
the air rapidly absorbs oxygen, and a dark color results. 

(c) A black urine is generally produced by unusually 
large amounts of those substances which cause a dark or 
smoky urine, particularly methemoglobin, melanin, and 
alcapton. 

(d) K bloody urine indicates the presence of normal 
blood and its pigment, oxyhemoglobin. A urine which has 
a slightly bloody tint should always be distinguished from 
one having a high color. 

{e) A blue VirmQ is of very rare occurrence. It is due to 
the presence of free indigo, a result of the decomposition 
of the indoxyl, which, in all such instances, is present in 
enormous quantity. Blue urine has been seen in cholera 
and rarely in typhus fever. When methylene-blue is taken 
into the stomach, it is absorbed and eliminated in the urine, 
to which it gives a marked blue or green color. 

(/) Urines having a greenish tint are occasionally seen, 
particularly after the use of an abundant quantity of milk, 
also in the inactive stage of a subacute glomerular ne- 
phritis, chronic diffuse nephritis, amyloid infiltration, and 
in some diabetic urines with a high percentage of sugar. As 
previously mentioned, a urine containing bile may, after the 
bilirubin has become oxidized, have a marked green color. 

iyg) The urine frequently has an abnormal color after 
the ingestion of certain vegetable substances, such as santonin, 
which imparts a yellow color, and rhubarb and senna, which 
cause a brown or reddish color. 

The following table of Halliburton^ shows the nature 
and origin of the chief variations in tint : 

Color. Cause of Color. Pathologic Condition. 

Nearly colorless. Dilution or diminution of Various nervous condi- 

normal pigments. tions, hydruria, dia- 

betes insipidus, granu- 
lar kidney. 
Dark yellow to Increase of normal or Acute febrile diseases, 

brown-red. occurrence of patho- 

logic pigments. 
Milky. Fat globules. Chyluria. 

Pus corpuscles. Purulent disease in urin- 

ary tract. 

1 For further information concerning alkapton see Neubauer u. Vogel, 
♦'Analyse des Harns," Bd. i, 1898, S. 243, 245; A. E. Garrod, "Lancet," 
Nov. 30, 190I. 2 "Chemical Physiology," 1841, p. 712. 



TRANSPARENCY. 



29 



Color. 
Orange. 

Red or reddish. 



Brown to brown- 
black. 



Greenish- yellow, 
greenish-brown, 
approaching black. 

Dirty green or blue. 



Brown-yellow to red- 
brown, becomes 
blood-red on addi- 
tion of alkalies. 



Cause of Color. 
Excreted drugs, e. g. , 

Unchanged hemoglobin. 

Pigments in food (log- 
wood, madder, bilber- 
ries, fuchsin). 

Hematin. 

Methemoglobin. 

Melanin. 

Hydrochinone and cate- 
chol. 

Bile pigments. 



A dark blue scum on sur- 
face with a blue de- 
posit, due to excess of 
indigo - forming sub- 
stances. 

Substances introduced 
into the organism with 
senna, rhubarb, and 
chelidonium. 



Pathologic Condition. 

Santonin, chrysophanic 
acid. 

Hemorrhage or hemo- 
globinuria. 



Small hemorrhages. 
Methemoglobinuria. 
Melanotic sarcoma. 
Carbolic acid poisoning. 



Jaundice. 



Cholera, typhus ; seen 
especially when the 
urine is putrefying. 



Transparency. — Freshly passed normal urine is gener- 
ally a perfectly transparent fluid ; as far as can be deter- 
mined by inspection, it is free from solid suspended mat- 
ter. After such a urine has stood a short time (one-half 
to four hours), however, a light flocculent cloud, consisting 
of mucus, cells, etc., will be found to occupy the center of 
the column of urine, and if the urine be not highly con- 
centrated, it usually settles to the bottom of the urine glass. 
This flocculent cloud is generally not sufficient to render 
the urine turbid. A perfectly normal, freshly passed urine, 
may, however, be turbid and have a milky appearance, due 
to a precipitation of earthy phosphates. Such a urine is 
frequently seen after a hearty meal, especially following the 
ingestion of vegetable food, and is the result of the elimina- 
tion of the alkaline salts of the food, — alkaline carbonates, 
— which render the urine neutral or alkaline, and precipitate 
the earthy phosphates ; it is perfectly physiologic, and 
usually of short duration, lasting only two to three hours, 
when the urine again becomes clear and transparent. A 
urine turbid from phosphates may be temporarily seen after 
every meal ; but, on the other hand, in some -individuals 
the after-meal urine is rarely, if ever, turbid from this cause. 
Any urine which is permanently turbid at the time it is 
voided may safely be considered pathologic. 



30 CONSTITUENTS OF NORMAL URINE. 

The total twenty-four-hour urine should in all cases be 
perfectly clear and transparent, A clear, freshly passed 
normal urine may, after it becomes cool, and especially if 
allowed to stand in a cool or cold place, become turbid by 
the separation of amorphous urates, which soon settle to the 
bottom of the glass and form an abundant, usually pink, 
sediment. This deposit of urates is most often seen in 
highly concentrated, although perfectly normal, urines. It 
may, however, be seen in the urines of disease, as in respi- 
ratory and circulatory diseases, acute febrile conditions, and 
also in the active stage of subacute glomerular nephritis. 
A deposit of amorphous urates is readily dissolved upon 
the application of heat. 

Bacteria frequently cause a marked turbidity in urines, 
and especially albuminous urines which have stood some 
time exposed to the air. The urine furnishes a favorable 
medium for the growth of bacteria, and often within twelve 
hours from the time the urine was passed it will be rendered 
very turbid. Such urines do not settle well, if at all, prob- 
ably owing to the constant motion of the bacteria. Fur- 
thermore, bacteria can not be removed by filtration through 
ordinary filter-paper, the filtrate being usually as turbid as 
the unfiltered urine. 

A urine which has undergone alkaline decomposition is 
generally rendered turbid by both bacteria and earthy 
phosphates ; such permanently alkaline urines should be 
distinguished from those temporarily alkaline (after-meal 
urines) ; the former being ammoniacal, while the latter are 
alkaline from fixed alkalies (absence of ammonia). 

A urine containing a large amount of pus is invariably 
turbid from the pus in suspension. Purulent urines also 
usually contain bacteria, which are either present when the 
urine is passed or grow very rapidly when the urine is 
allowed to stand exposed to the air. 

Chyle in the urine causes a milky turbidity, due to the 
presence of very finely divided fat. Such a urine is of rare 
occurrence. (See Chyluria.) 

Odor. — Normal urine usually has a pleasant, aromatic 
odor, due, it is believed, to the presence of extremely small 
quantities of volatile acids — phenylic, taurylic, damaluric, 
and damolic acids. This aromatic odor is most marked in 
urines which are concentrated. The so-called *' urinous 
odor" is due to the products of decomposition, and is a 
putrescent, repulsive odor, in which ammonia is plainly dis- 



REACTION. 31 

tinguishable ; all urines, if allowed to decompose, have a 
urinous odor. An ammoniacal or urinous odor is only im- 
portant when it is present at the time the urine is passed, 
thus showing that the urine has decomposed inside the 
body. When a urine containing a large amount of albumin 
or a large quantity of pus decomposes, it may evolve the 
odor of sulphuretted hydrogen, which is formed from the 
sulphur in the albuminous matter. The HgS in ammoni- 
acal urine combines with the ammonium to form ammo- 
nium sulphide, hence the combined odor of sulphuretted 
hydrogen and ammonium. 

A strong odor of sulphuretted hydrogen to the urine 
may accompany the evacuation of an abscess, located in the 
region of the intestine, into the urinary tract ; a purulent 
urine from this cause usually has also a distinct fecal odor. 
When urines containing cystin decompose, HgS is evolved, 
formed from the sulphur in the cystin. 

The urine frequently has a peculiar odor after the inges- 
tion of certain vegetable substances and certain drugs ; 
thus, it has a characteristic odor after eating asparagus, 
and an odor of violets following the inhalation of the 
vapor of oil of turpentine, or following its absorption from 
the skin or digestive tract. The absorption of terebene 
gives to the urine the same odor of violets. The urine has 
a peculiar odor after the use of copaiba, sandalwood oil, 
cubebs, tolu, etc. 

The odor of the freshly passed urine is of very little clin- 
ical importance, excepting in those instances in which it is 
ammoniacal or evolves the odor of sulphuretted hydrogen. 

Reaction. — The reaction of the normal, twenty-four- 
hour, mixed urine is always acid. This acidity is due 
to acid sodium phosphate (monosodic acid phosphate, 
NaH^PO^). It is believed that the monosodic acid phos- 
phate of the urine is partly derived from a chemic combi- 
nation taking place between the disodic acid phosphate 
(Na2HP04, neutral or alkaline in reaction) in the blood, 
and uric acid, also in the blood, according to the following 
equation : 

Na2HP04 + H^CjH.N^Os = NaH^PO^ + NaHQH^NPg. 

It was formerly supposed that traces of uric and hippuric 
acids contributed to the acidity of the urine, but such is 
probably not the case, as has been showii by the experi- 



32 CONSTITUENTS OF NORMAL URINE. 

ments of Voit, Huppert, Briicke, and others, who found 
that both uric and hippuric acids existed in combination, 
the former as a urate and the latter as a hippurate. 

The degree of acidity varies considerably at the different 
hours of the day, and particularly with the length of time 
before or after taking food. Usually, a specimen of urine 
passed at any time of day is acid, excepting after a meal, 
when it may be temporarily neutral or alkaline from fixed 
alkalies — alkaline carbonates — which are derived from the 
salts ingested with the food. This temporary change in 
the reaction is sometimes called the alkaline tide, beginning 
with a gradual diminution of the acidity, then becoming 
neutral or alkaline, reaching its height in from two to four 
hours, and finally becoming acid again. This is a physi- 
ologic condition occurring in individuals who are perfectly 
healthy. Such a urine is generally turbid from the deposit 
of earthy phosphates ; the addition of a few drops of acetic 
acid to the urine will readily cause the turbidity to disappear 
entirely. The urine may be highly acid, especially after 
a fast, — for instance, before breakfast, — when it is usually 
found to be concentrated, having a high specific gravity and 
high color. Under normal conditions the freshly passed 
urine may be faintly acid, normally acid, or strongly acid, 
and in a general way it may be said that, with the excep- 
tion of the after-meal urine, the degree of acidity depends 
largely upon the concentration — that is, if dilute, it is faintly 
acid, and if highly concentrated, strongly acid. 

A urine that is acid when passed, upon standing exposed 
to the air for from six to twelve hours, often becomes more 
acid ; this phenomenon has been termed acid fermentation. 
This increased acidity has been ascribed by Sherer to the 
presence of lactic and acetic acids, formed by the decompo- 
sition of the coloring-matters of the urine ; the decompos- 
ing element being mucus, which acts as a ferment. This 
explanation has not been satisfactorily proved, however, 
while the increased acidity is by no means constant. A 
urine that has undergone this so-called acid fermentation 
is usually higher in color than when it was passed, and is 
very likely to contain crystals of acid urates or uric acid. 
If such a urine is allowed to stand a longer time, it begins 
to lose its acidity and finally becomes alkaline. _ 

The alkalinity of the urine is due either to fixed alkalies, 
— sodium or potassium carbonates, — as has already been 



Plate 2 




Sediment of Alkaline Fermentation (after Hofmann and 
Ultzmann). 



REACTION. 33 

shown, or to the product of alkaline decomposition — 
ammonium carbonate formed from the decomposition of the 
urea. When the urea is acted upon by the ureafermenty it 
takes up two equivalents of water, and results in ammonium 
carbonate. Thus : 

CH.N^O + 2Hp = (NHJ^COg. 

Such a urine has an ammoniacal or ''urinous" odor, 
giving off free ammonia, in contradistinction to one alka- 
line from fixed alkalies in which no ammonia is evolved. 
A urine that has undergone alkaline decomposition is 
usually very turbid, partly from the large number of 
bacteria present, and partly from the deposit of amor- 
phous phosphates of calcium and magnesium, and crystal- 
line elements — notably ammonio-magnesium phosphate 
(triple phosphate), and frequently ammonium urate. (See 
Plate 2.) If the urine is allowed to stand undisturbed, its 
surface may be covered with a film, composed of bacteria 
and a vegetable growth, in which crystals of ammonio- 
magnesium phosphate and ammonium urate are often en- 
tangled. Although this alkaline decomposition is most 
often seen after the urine has been allowed to stand in the 
air (natural decomposition), it may be found to have taken 
place inside the body, particularly in certain chronic inflam- 
matory processes in the bladder, into which the urea fer- 
ment has gained access ; the freshly passed urine then has 
a strong ammoniacal odor and alkaline reaction. 

Normal urine may have an amphoteric reaction, — /. e.y 
the same urine may change blue litmus paper red, and red 
litmus paper blue, — because of the simultaneous presence 
in the urine of variable proportions of acid and neutral 
salts. 

Causes of Diminished Acidity. — i. After a full meal, 
and particularly following the ingestion of a vegetable diet. 
In vegetarians, as in herbivora, the food contains an excess 
of alkahne salts with vegetable acids, such as tartaric, malic, 
citric, succinic, etc. These acids are converted to carbon- 
ates, which, passing into the urine, give it a neutral or alka- 
line reaction. 

2. Following the discharge of the gastric juice from the 
stomach, as by vomiting or through a gastric fistula. 

3. After the administration of considerable quantities of 
alkaline carbonates, alkaline phosphates, or caustic alkalies. 

3 



34 CONSTITUENTS OF NORMAL URINE. 

4. Decomposition of the urine (alkaline fermentation), 
the urea being converted into ammonium carbonate. 

Causes of Increased Acidity. — i. Exclusive meat diet. 

2. After hot baths and free perspiration. 

3. Excessive muscular exercise with free perspiration. 

4. Internal administration of acids, such as benzoic or 
boric acids. 

5. The presence of free fatty acids resulting from patho- 
logic conditions. 

Specific Gravity. — The specific gravity of normal urine 
is 102 1 for an average amount of 1500 c.c. in the twenty- 
four hours. This means that, taking distilled water at 15.5° 
C. (60° F.) as I, each cubic centimeter of the urine weighs 
1.02 1 grams ; or taking distilled water as 1000, each cubic 
centimeter of the urine weighs 102 1 grams. The specific 
gravity gives the relative proportion of solid matter in the 
urine ; then, by knowing the total twenty-four-hour quan- 
tity of urine, an approximate idea of the absolute solids is 
obtained by multiplying the last two figures of the specific 
gravity by 2.33. (See p. 40.) Under normal conditions 
the specific gravity may vary between 10 1 8 and 1 02 5, such a 
variation being dependent chiefly upon the total twenty- 
four-hour amount of urine, the quantity and character of 
the food ingested, and the rapidity of tissue waste. Thus, 
a urine dilute from taking a large quantity of liquid may 
have a specific gravity of 10 18, or as low as 1012 ; and, on 
the other hand, a concentrated urine following copious per- 
spiration may have a specific gravity of 1025, or as high as 
1030, and be passed by a perfectly healthy individual. 
Such variations from the normal are usually temporary ; 
if permanent, they are usually pathologic. Nitrogenous 
food, such as meat, increases the solid matter in the urine, 
and hence raises the specific gravity to a greater or less 
degree. 

Under pathologic conditions there is a marked variation 
in the specific gravity, particularly in diseases of the kid- 
neys, but also frequently in diseases in other parts of the 
body ; for example, in chronic interstitial nephritis and in 
diabetes insipidus the specific gravity may be as low as 
100 1 or 1002 ; and, again, in diabetes mellitus it may go 
as high as 1050. In most diseases of the kidney there 
is a tendency toward a low specific gravity, although it 
may be normal or even high. If a normal or pale colored 



SPECIFIC GRAVITY. 33 

urine has a specific gravity of 1030 or more, the presence 
of sugar is strongly suggested ; but, on the other hand, 
sugar may be present with a low specific gravity (as low as 
loio) ; hence the importance of testing every specimen of 
urine for sugar, regardless of the specific gravity. 

In albuminous urines, especially those containing one- 
eighth of one per cent, or more, the specific gravity is always 
more or less affected by the albumin in solution — that is, it 
is raised higher than it would be if only normal urinary 
constituents were present. 

The specific gravity of the urine is also influenced by 
certain drugs : for example, following the administration of 
large doses of potassium acetate, the specific gravity may 
be 1020, the total twenty-four-hour quantity increased to 
2000 c.c. or more, and the normal urinary constituents not 
increased. In such a case it is the presence of the 
increased amount of the potassium salts that affects the 
specific gravity. 

The urinometer is undoubtedly the most convenient 
means of determining the specific gravity of the urine. 
This instrument is less accurate than the balance (Westphal 
or Mohr) and pycnometer, although for practical purposes 
it is sufficiently accurate if it is properly constructed. 
Every urinometer should be carefully tested with distilled 
water at 60° F. (15.5° C), in which it should read o or 
1000. A large number of urinometers are on the market, 
some of which vary several points from the standard, but 
those constructed by E. R. Squibb & Sons, of Brooklyn, 
New York, are among the most accurate. (Fig. i.) They 
are very carefully standardized at JJ^ F. (25° C), — a tem- 
perature much more usual than 60'^ F. (15.5° C), — and 
with each urinometer a thermometer is furnished for tem- 
perature corrections. In ordinary work the use of the 
thermometer is unnecessary, since the variations by changes 
in temperature are usually only slight (a variation in the 
reading of four is the maximum error which can occur at any 
temperature at which urine is likely to be tested — Tyson). 

A urinometer-glass should be used whenever the specific 
gravity is to be taken. Such a glass is usually supplied 
with each urinometer, but the one used by the author (Fig. 
2) is strongly recommended. ^ This urinometer-glass has the 

1 Manufactured by Richard Briggs Co., 287 Washington St., Boston. 



36 



CONSTITUENTS OF NORMAL URINE. 



advantage of having a wide foot, perfectly parallel sides, 
and a well-formed lip, not usually found in the ordinary 
urinometer-glass. The glass made by E. R. Squibb & 
Sons has the added advantage of being fluted on the 
sides. 

In case the specimen of urine is too small for the specific 
gravity to be taken in the urinometer-glass a sufficiently 
large test-tube may be used, but such a tube should not be 
too small in relation to the urinometer ; nor should the 
latter be allowed to impinge against one side of the glass, 
lest, in consequence of the capillary attraction between the 




I 




Fig. I. — Squibb's urinometer. 



Fig. 2.— Urinometer and urinometer-glass 
(slightly smaller than one-half actual size). 



tube and the urinometer, the latter should not sink to the 
proper level. The urinometer should be introduced into 
the tube containing the urine, allowed to find its proper 
level, and the reading taken ; the urinometer should then 
be forced down into the urine, allowed to rise until it again 
reaches its proper level, and a second reading taken. The 
two readings should be exactly the same. Any discrepancy 
in the readings shows that in either one or the other obser- 
vation the urinometer impinged against one side of the 
tube, from which it is readily freed by moving it gently from 
side to side. 



SPECIFIC GRAVITY. 37 

Method of Taking Specific Gravity by the Urinome- 

ter. — Fill the urinometer-glass three-fourths full of urine ; 
introduce the urinometer, pushing it down into the urine so 
that it just touches the bottom of the urinometer-glass, 
then release it and wait until it finds the correct level ; when 
it comes to a rest, the scale is read off through the fluid 
from below upward, the last mark seen below the surface 
(at the meniscus) being the correct specific gravity. The 
reading should not be taken from above the surface of the 
fluid, since the capillary attraction of the fluid on the shaft 
of the urinometer causes an error of from one to two grad- 
uations on the scale. 

If the quantity of urine is too small to fill sufficiently the 
cylinder, it may be diluted with enough distilled water to 
fill the cylinder to the required height, noting the volume 
added. From the specific gravity of this mixture may be 
calculated that of the urine. Thus, suppose it is necessary 
to add four times as much water as urine to enable us to 
use the urinometer — that is, to make five volumes — and 
the specific gravity of the mixed fluid is 1004, then that of 
the urine will be 1000 + (4x5)= 1020. Although the 
principle of this method is correct, — and the results must 
be if the data are, — the urinometers in use are not usually 
so finely graduated that absolute accuracy in reading is 
secured, while any error in reading is multiplied by the 
number of volumes used. Hence, it is desirable to use this 
method as rarely as possible, especially with urine of low 
specific gravity. 

Solids. — The term "soKds," as ordinarily applied, refers 
to the normal constituents of the urine present in solution, 
such as urea, chlorides, uric acid, phosphates, sulphates, 
ethereal sulphates, and various other constituents present 
in smaller quantities. 

" Relative " and " Absolute " Solids. — The term rela- 
tive solids applies to the proportion of solid matter to that 
of thcL water which contains it : for example, the relative 
quantity of urea is normally two per cent. — that is, two 
parts of urea in one hundred parts of urine. The absohtte 
solids are the solids contained in the total twenty-four-hour 
urine, calculated in grams or grains : for example, the 
absolute quantity of urea is normally thirty-three grams — 
that is, the total quantity of urea in twenty-four hours. 

The specific gravity of the urine affords a general idea of 



38 CONSTITUENTS OF NORMAL URINE. 

the total solids present, but that in itself is not sufficient. 
It is therefore necessary, first, to obtain the relative propor- 
tion of the most important constituents, — as urea, chlorides, 
phosphates, sulphates, uric acid, etc., — and, second, to de- 
termine the absolute quantities of these solids, before infer- 
ences can be deduced therefrom. Observations concerning 
the solids of the urine should be made upon a sample of 
the mixed twenty-four-hour secretion, and not on the urine 
of a single micturition. 

Under normal conditions the total solids amount to from 
seventy to seventy-three grams in twenty-four hours, of 
which urea constitutes nearly one-half, the chlorides about 
one-fifth, and the phosphates about one-twenty-fifth. The 
absolute quantity of urea, being the most abundant solid 
of the urine, is of the greatest importance in judging of the 
capability of the kidneys for work, and also the extent of 
tissue metabolism in both health and disease. The abso- 
lute quantities of chlorine and phosphoric acid are also 
important in some cases in completing the picture of the 
urine. 

The actual quantity of solids in the urine, particularly 
the total quantities of each of the most important constitu- 
ents, having been ascertained, in order to make valuable 
deductions therefrom in health or disease it is necessary to 
take into consideration the weight, age, habits, diet, sur- 
roundings, and the nature of the disease in each individual 
case before deciding as to the extent of the increase or 
diminution of the solids for a given individual. For ex- 
ample, on an average mixed diet, a large adult male nor- 
mally excretes a larger quantity of solids than a small adult 
male (the average for a person of 66 kilograms being 
from 66 to 75 grams, of which urea equals from 35 
to 40 grams) ; and a large adult female, a larger quantity 
than a small adult female (the average for a person of 5 5 
kilograms being from 60 to 70 grams, of which urea 
equals from 25 to 35 grams). In persons between fifty and 
seventy years of age the total solids fall materially in health. 
In healthy children, although the total solids are far below 
the average for an adult, they are larger in proportion to 
the height, age, and weight than in the adult. Much de- 
pends also on the diet — that is, a person ingesting an 
abundance of nitrogenous food will excrete larger quanti- 
ties of solids, especially urea. On the other hand, when a 



TOTAL SOLIDS. 39 

meager diet, or one consisting chiefly of milk, is taken, the 
sohds are usually diminished. 

In most chronic diseased conditions the solids are more or 
less diminished, whether the disease be in the kidneys or in 
some other organ or organs of the body, and particularly 
when the patient is not capable of taking or assimilating a 
mixed diet. The total solids are notably diminished in ad- 
vanced chronic diseases of the kidney, in which the functions 
of these organs are greatly interfered with on account of the 
diseased epithelium lining the renal tubules. A marked 
reduction of the solids in renal disease often indicates a 
tendency to uremia, although this dangerous complication 
may arise when the solids are normal or only slightly dimin- 
ished. In the early stages of acute fevers the solids may, 
for a short period, be normal or increased, but usually at 
the expense of the tissues (increased metabolism), whereas, 
later, they are markedly diminished. During the conva- 
lescence, however, they usually reach the normal, or are 
increased. In diabetes mellitus .and insipidus the total 
solids (aside from the sugar in the former disease) are gen- 
erally increased. 

Determination of Total Solids. — The total solids of the 
urine may be determined in the following ways : 

1. Take five cubic centimeters of the mixed twenty-four- 
hour urine in a previously dried and weighed platinum or 
porcelain dish. Evaporate it in a vacuum over sulphuric acid. 
After twenty-four hours remove this sulphuric acid and re- 
place by fresh acid ; exhaust again, and weigh after an- 
other twenty-four hours. Deduct the weight of the dish, 
and the remainder gives the solids in five cubic centimeters 
of urine. From this the solids in the whole volume of 
urine are readily calculated. This method is one of the 
most accurate for the determination of the solids of the 
urine. 

2. A quicker method is to evaporate to dryness over a 
water-bath a given quantity of urine — say twenty-five cubic 
centimeters — in a previously dried and weighed porcelain 
dish. Dry the residue by placing the dish in an oven at i io° 
C. (230° F.) for a few hours ; cool and weigh. This should 
be repeated several times until no further loss of weight 
occurs from drying. Subtract the weight of the dish, and 
the remainder will represent the solids in twenty-five cubic 
centimeters of the urine. This method, however, is not 



40 CONSTITUENTS OF NORMAL URINE. 

VQvyr accurate, as some of the compounds in the urine are de- 
composed at a temperature of iio° C. (230° F.). 

J. To Determine the Solids in the Twenty-four-hour Uri?ie 
by Means of the Specific Gravity. — Knowing the quantity of 
urine passed in twenty-four hours and its specific gravity, an 
approximate estimation of the total quantity of soHd matter 
may be readily obtained by multiplying the last two figures 
of the specific gravity by the arbitrary coefficient of 
Haeser, 2.33. This will give the approximate number of 
grams of solids in 1000 c.c. of the urine. For example, 
suppose the twenty-four-hour urine to be 1350 c.c, and 
the specific gravity to be 1024, then 

24 X '^•ZZ = 55-92 grams in looo c.c. 

Since the total quantity of urine in twenty-four hours is 
1350 c.c, it will contain 

55.92 X 1350 

1000 : 1350 : : 55.92 : x, = ^Q,^ = 75-49 grams 

in twenty-four hours. -This result indicates that a trifle 
more than the average normal quantity of solids has been 
excreted. 

While this method of arriving at the quantity of solids is 
not sufficiently accurate for scientific purposes, it is often of 
considerable value for clinical purposes. It should be borne 
in mind, however, that if the urine contains solid matter other 
than the normal constituents, the solids obtained by this 
method will often be found to be very high. For example, 
in case of diabetes mellitus they will be found to be above 
the normal, due to the presence of the sugar ; highly 
albuminous urines may have increased total solids, due to 
the quantity of albumin present. So also, after the use of 
certain drugs, such as the potassium salts, — viz., acetate, 
citrate, bitartrate, etc., — the solids will be considerably 
above the normal, because of the presence of these salts. 



CHAPTER II. 
ORGANIC CONSTITUENTS OF NORMAL URINE. 

UREA. 

CH4N2O. 

Urea is the chief organic constituent of the urine. It is 
isomeric with ammonium cyanate, from which it was first 
prepared synthetically by Wohler. It may also be prepared 
by the action of ammonia on carbonyl chloride, by hydra- 
tion of cyanamide, and from ammonium carbonate. 

Urea is readily soluble in alcohol and water, but insoluble 
in ether. It is odorless, has a salty taste, and its solution 
has a neutral reaction. Urea crystallizes in colorless four- 
or six-sided prisms with oblique ends, or, when rapidly crys- 
tallized, in delicate, white, silky needles. When treated 
with nitric acid, nitrate of urea — CON2H^,HN03 — is formed, 
which crystallizes in octahedral, hexagonal, or lozenge- 
shaped plates. These plates are usually arranged in strata, 
although occasionally seen singly (Fig. 3), and are less 
soluble in water than urea crystals. With oxalic acid urea 
unites to form oxalate of urea, — (C0N2HJ2» H^2Q^4 + ^2^' 
— which is in the form of flat or prismatic crystals. 

• Other compounds of urea with acids have also' been de- 
scribed ; thus, phosphate of urea, C0N2H^, HgPO^, was 
said by Lehmann ^ to occur in small quantities in urine ; a 
compound of urea with uronitrotoluolic acid — with the 
■formula Cj^H^gNgO^^ — was found by Jaffe 2 in dogs' urine 
after the administration of orthonitrotoluol ; the greater 
part of the urea in urine is, however, free. 

Urea also forms compounds with salts, the most impor- 
tant being with mercuric nitrate. With this substance it 
forms a white precipitate having the formula CONgH^ . Hg- 
(-^03)2 • 3HgO. This compound is important, as Liebig's 

1 *< Chemische Centralblatt," 1866, S. 1119. 

2 "Zeitschrift fiir physiologische Chemie," II, 50. 

41 



42 ORGANIC CONSTITUENTS OF NORMAL URINE. 

volumetric process for the estimation of urea is based on 
its formation. 

There is also a crystalline compound of urea with sodium 
chloride, C0N2H^ . NaCl + H2O, which may be obtained 
by evaporating to dryness a solution of these two sub- 
stances, such as occurs, for instance, in ordinary urine. 
Urea may be decomposed in various ways : 
I. When heated to from 150° to 170° C, it melts and 
gives off ammonia ; the substance which remains is termed 
biuret.^ 

2CON,H,-NH3 = CAN3H,. 
Urea. Biuret. 

Biuret with caustic potash and copper sulphate gives a 




Fig- 3-— Crystals of nitrate of urea (upper half) and. oxalate of urea (lower half) 

(after Funke). 



characteristic rose-red solution. When biuret is heated, it 
gives off ammonia, and cyanuric acid is left — 

3C,0,N3H5 - 3NH3 .== 2C3H3N3O,. 

Biuret. Cyanuric acid. 

Cyanuric acid gives a violet solution with caustic potash 
and copper sulphate. 

2. By means of an organized ferment, the torula, or micro- 
coccus ureae (which grows readily in stale urine), urea takes 
up water, and is converted into ammonium carbonate — 
CON^H, -f 2Hp = (NHJ2CO3. 

1 "Poggendorf s Annalen," Lxxiv, 67. 



UREA. 43 

3. By means of nitrous acid urea is broken up into car- 
bonic acid, water, and nitrogen — CON2H^ + ^2^3 "^ ^^2 
+ 2H3O + 2N2. 

4. Chlorine water causes a somewhat similar decomposi- 
tion— CON.H, + H^O + 3CI2 = CO2 + N2 + 6HCL 

5. Hypochlorite or hypobromite of soda decomposes 
urea in the following way : C0N2H^ + 3NaOBr = COg 
-\- N., +2H.,0 + 3NaBr. This reaction is important, as 
upon it is based one of the best methods of estimating the 
quantity of urea in urine. (See p. 50.) 

Since urea is the chief organic constituent of the urine, 
it is a fair index of the excretion of nitrogenous matter from 
the body. Not all of the nitrogen, however, is excreted as 
urea, as veiy small amounts of it go out as uric acid, 
xanthin, hypoxanthin, sarkin, kreatinin, allantoin, etc. 

Much discussion has arisen in the past in relation to the 
formation of urea — especially where it is formed and from 
what it is formed. As first pointed out by Meissner,^ urea 
is probably formed chiefly in the liver. This view has 
been confirmed by the more recent experiments of Brou- 
ardel,2 Roster,^ Schroeder,^ and Minkowski.^ It is also 
probable that the spleen and lymphatic and secreting glands 
participate in the formation of urea. The urea passes into 
the blood, and is carried to the kidneys, where it is excreted. 
Contrary to the early belief, urea is not formed in the kid- 
neys, or, if at all, only in minute quantities, as was first 
demonstrated by Prevost and Dumas, ^ who found that the 
formation of urea continued, accumulating in the blood and 
tissues, even after the complete extirpation of the kidneys. 
Similarly, in extensive disease of the kidneys in which 
there is almost complete suppression of urine, urea con- 
tinues to be formed and collects in the organism. Further- 
more, in support of this view we find that in extensive de- 
generative changes in the liver, as in acute yellow atrophy, 
the formation of urea is greatly diminished. On the other 
hand, in those diseases of the liver in which the activity of 
the liver-cells is greatly increased, as in diabetes mellitus, 
the urea formation is increased. 

1 " Zeit. f. rat. Med.," N. F., xxxi, 234. 

2 " Archiv de physiol. norm, et pathol.," [2] ill, 373, 551. 

3 Quoted by Hoppe-Seyler, " Physiol. Chem.," S. 807. 

4 "Lud wig's Festschrift," 1887, S. 89. 

5 ''Ann. de Chim. et de Physiol.," xxiii, 90. 



44 ORGANIC CONSTITUENTS OF NORMAL URINE. 

The quantity of urea eliminated in twenty-four hours 
varies considerably, the chief cause of variation being the 
amount of proteid food ingested, together with the rapidity 
of tissue metabolism in health or disease. In a man who 
is in a state of equilibrium, and on an ordinary mixed diet, 
the quantity of urea excreted daily is between 25 and 40 
grams, the average being about 33 grams (500 grains). On 
a diet poor in nitrogenous matter it may fall to from 1 5 to 
20 grams ; and, on the other hand, on a diet rich in nitrogen 
it may rise to from 60 to 80 grams per diem. The per- 
centage of urea varies considerably ; it may be roughly 
said that the average relative quantity in health is two per 
cent. ; but the percentage usually varies with the concentra- 
tion of the urine. 

Women excrete rather less urea than men ; children less, 
absolutely, than adults, but more in proportion to their 
weight. Uhle gives the following table, which represents 
the quantity of urea excreted in twenty-four hours per kilo- 
gram of body -weight at different ages : 

From 3-6 years, about I gram. 

" 8-11 " "0.8 " 

" 13-16 " .• • • " 0.4-0.6 <* 

Adults, *' 0.37-0.6 " 

From this it is seen that, per kilogram weight, children up 
to eleven years of age excrete about twice the quantity of 
urea that adults do, and after eleven years practically the 
same as adults. 

An Increased Quantity of Urea. — (a) In health the 
absolute quantity of urea may be increased by (i) a 
hearty mixed diet. (2) Strenuous exercise causing in- 
creased metabolism ; and it is for this reason that the quan- 
tity of urea is greater during the day than during the night : 
the average proportion of the day to the night urea being 
as three is to two. (3) By the ingestion of ammonium 
compounds, particularly ammonium chloride, it having been 
found that practically nine-tenths of the nitrogen in the 
ammonium chloride is eliminated as urea. (4) By the in- 
gestion of large quantities of water, the metabolism being 
increased thereby, especially when an abundance of water is 
taken for a short time. If this ingestion is continued for a 
long time, the metabolism is diminished, and hence there is 
a diminution in the urea. (5) Following hot baths the urea 
may be increased. 



UREA. 45 

(b) In disease the absolute quantity of urea is in- 
creased (i) in the early stages of acute febrile diseases, the 
increase being due largely to the increased metabolism of 
the tissues, which, together with the ingestion of very little 
food, results in emaciation. One notable exception to this, 
however, is in acute diseases associated with increasing 
dropsy, as in acute nephritis ; also those accompanied by 
exudations into other parts of the body, as in cholera ; and 
other acute intestinal diseases in which there is marked 
diarrhea. (2) During the convalescence from acute dis- 
eases associated with dropsy the urea may be increased 
during the time that the dropsical fluid is being reabsorbed. 
Such an increase, however, is usually only temporary, 
and after all of the dropsical fluid has been absorbed the 
urea falls below the normal, as is the rule in convalescence 
from other acute diseases. (3) In intermittent fever the 
urea is increased before the patient has a chill, but dimin- 
ished afterward. (4) In diabetes insipidus the urea is much 
increased absolutely (may go as high as 130 grams), the 
twenty-four-hour quantity of urine being very large, but 
the specific gravity very low. (5) In diabetes mellitus, on 
account of the increased metabolism, the total urea is 
usually above the normal. (6) In chronic interstitial neph- 
ritis, although the absolute quantity of urea is usually 
diminished, it may, in rare instances, be absolutely in- 
creased. This has been occasionally observed in children 
by the writer, where, at the autopsy, the disease was found 
to exist to a marked degree. (7) In chronic gout the urea 
may be increased to fifty or sixty grams in twenty-four 
hours. 

A Diminished Quantity of Urea. — (a) In health the 
urea is diminished absolutely (i) whenever very little nitro- 
genous food is taken — seen especially in vegetarians ; also 
in those instances in which the individual takes very little 
food of any kind. (2) Sometimes, following very free per- 
spiration, the urea is diminished absolutely on account of 
the elimination of a certain amount of this substance by 
the sweat-glands. (3) In many instances of normal preg- 
nancy the total urea is diminished. This is explained on 
the ground that the nitrogenous elements ingested go to 
nourish the fetus. The average amount of urea in normal 
pregnancy is about twenty grams in twenty-four hours. 
(4) Following the administration of small doses of quinine 



46 ORGANIC CONSTITUENTS OF NORMAL URINE. 

(Oppenheim) the urea is low, although not markedly dimin- 
ished. (5) The long-continued ingestion of excessive 
quantities of water results in more or less reduction in the 
total quantity of urea. 

(b) In disease the urea is generally diminished, the ex- 
tent of the diminution being usually dependent upon, first, 
the degree of diminished metabolism, and, second, the capa- 
bility of the kidneys to excrete the urea. ( i) In most diseases 
of the kidneys — especially the advanced chronic forms, such 
as chronic interstitial, chronic diffuse, and subacute glomer- 
ular nephritis — the urea is usually markedly diminished. 
In amyloid infiltration it may be normal or diminished, but 
usually not so much diminished as in chronic interstitial 
nephritis, since in the former disease the infiltration takes 
place about the blood-vessels, and consequently does not 
interfere with the secreting structure of the kidney until very 
late. On the other hand, in chronic interstitial nephritis the 
secreting portion of the kidney is affected much earlier in 
the disease. Not infrequently a determination of the abso- 
lute amount of urea is of considerable aid in the differential 
diagnosis of these two forms of Bright's disease. In the 
first two stages of acute nephritis the urea, absolutely, is 
much below the normal, especially in the first stage or at 
the time when the dropsy is increasing. (2) In the func- 
tional disturbances of the kidneys — active and passive 
hyperemias — the urea is frequently diminished, the extent 
of the diminution being largely dependent upon the cause 
of the disturbance. (3) In acute febrile diseases following 
the acme of the disease the quantity of urea is low, and 
likewise during the convalescence from these diseases, since 
the nitrogenous elements go to build up the tissues. (4) In 
all diseases attended with extensive dropsy the urea is dimin- 
ished up to the time the effusion begins to be reabsorbed, 
when it gradually increases. (5) Shortly before death from 
any cause the urea is usually markedly diminished (five to 
six grams in twenty-four hours), more especially in chronic 
kidney diseases. In those cases in which the degeneration 
of the renal tissue is veiy extensive and the kidneys are 
not capable of excreting the urea, the elimination may 
take place through other glands, notably the sweat-glands. 
In such instances the skin, especially in the axillae and 
groins, has been found to be covered with a coating of 
crystallized urea. (6) Extensive vomiting, and (7) marked 



DETECTION OF UREA. 47 

cases of diarrhea cause a diminution in the amount of the 
urea eHminated ; this is particularly true in connection with 
extensive renal disease, a portion of the urea being elim- 
inated by these channels. (8) In all degenerative changes in 
the liver there is very low urea, probably the result of the 
greatly reduced metabolism of the liver. 

Detection. — The presence of urea may be detected in 
the following ways : 

1. Place a drop of the urine on a watch-glass or glass 
slide, add one drop of pure nitric acid (the yellow nitric 
acid should be avoided), and allow the mixture to evapo- 
rate spontaneously in the air. If urea be present, crystals 
of nitrate of urea will be seen when examined with the 
microscope. 

2. To a drop of the urine add a drop of a saturated solu- 
tion of oxalic acid. If urea be present, crystals of oxalate 
of urea form, which, under the microscope, appear in the 
form of rhombic plates, or short, thick, rhombic prisms. 

3. To the urine add an equal volume of sodium hypo- 
bromite or hypochlorite, and if urea be present, the evolu- 
tion of nitrogen gas takes place. 

4. Place a few crystals of urea in a test-tube, and heat to 
melting ; then add a few drops of sodium or potassium 
hydrate and a drop or two of a dilute solution of sulphate 
of copper. The biuret reaction occurs, which consists of a 
violet or a rose-red color. 

5. To a crystal of urea about the size of the head of a 
pin add one drop of a moderately concentrated solution 
of furfurol, and then a drop of concentrated hydrochloric 
acid, and heat. A play of colors results : a yellow, green, 
blue, violet, and, finally, in the course of a few minutes, a 
purple-violet (furfurol reaction of Schiff i). 

Quantitative Determination of Urea. — Various 
methods have been suggested for the quantitative determina- 
tion of urea. Of these, the three following are most suit- 
able: («) The mercuric nitrate or Liebig's method; (d) 
the hypobromite or hypochlorite method ; (c) Morner- 
Sjoqvist method. 

(a) Liebig's Method. — If albumin be present, it must first 
be removed by coagulation (heat). The combination between 
urea and mercuric oxide, which is (CON2H^)2Hg(N03)2 . 3HgO, 

1 "Berichte d. Chem. Gesellsch.," x, 773, 1887. 



48 ORGANIC CONSTITUENTS OF NORMAL URINE. 

results in a white precipitate, insoluble in water and weak 
alkaline solutions. It is, therefore, necessary to prepare a 
standard solution of mercury, and to have an indicator by which 
to detect the point when all the urea has entered into combina- 
tion with the mercury, and the latter slightly predominates. 
This indicator is sodium carbonate, which gives a yellow color 
with the excess of mercury, owing to the formation of hydrated 
mercuric oxide. 

Theoretically, loo parts of urea should require 720 parts of 
mercuric oxide; but practically, 772 of the latter are necessary 
to remove all the urea, and at the same time show the yellow- 
color with alkali ; consequently, the solution of mercuric nitrate 
must be of empiric strength in order to give accurate results. 

The following solutions must be prepared : 

1. Standard Mercuric Nitrate Solution: Dissolve 77.2 grams 
of red oxide of mercury (weighed after it has been dried over 
a water-bath), or 71.5 grams of the metal itself, in dilute nitric 
acid. Expel the excess of acid by evaporating the liquid to a 
syrupy consistence. Alake up to 1000 c.c. with distilled water, 
adding the water gradually. This solution is of such strength 
that 19 c.c. will precipitate 10 c.c. of a 2 per cent, urea solu- 
tion. Add 52.6 c.c. of water to the liter of the mercuric nitrate 
solution, and shake well; then 20 c.c. (instead of 19) = 10 c.c. 
2 per cent, urea solution — /. e., i c.c. =0.01 of urea. 

2. Baryta Mixture: This is a mixture of two volumes of 
solution of barium hydrate with one of solution of barium 
nitrate, both saturated in the cold. 

A?ialysis. — Take 40 c.c. urine; add to this 20 c.c. of baryta 
mixture, and filter off the precipitate of baryta salts (phosphates 
and sulphates); take 15 c.c. of the filtrate (this corresponds to 
10 c.c. of urine) in a beaker. Run into it the mercuric nitrate 
solution from a burette, until, on mixing a drop of the mixture 
with a drop of a saturated solution of sodium carbonate on a 
white tile, a pale lemon color appears. Then read from the 
burette the amount used, and calculate from this the percentage 
of urea. 

Corrections. — This method approaches accuracy only when 
the quantity of urea present is about 2 per cent., which is about 
the normal percentage of urea in urine. The chlorine in the 
urine must also be estimated, and the quantity of urea indicated 
reduced by the subtraction of i gram of urea for every 1.3 
grams of sodium chloride found. If the urine contains less 
than 2 per cent, of urea, o.i c.c. of mercuric nitrate solution 
must be deducted for every 4 c.c. used; if more than 2 per 
cent, of urea, a second titration must be performed with the 
urine diluted with half as much water as has been needed of 
the mercurial solution above 20 c.c. Suppose, then, 28 c.c. 



QUANTITATIVE DETERMINATION OF UREA. 49 

have been used in the first titration, the excess is 8 c.c; there- 
fore 4 c.c. of water must be added to the urine before the 
second titration is made. When ammonium carbonate is present, 
first estimate the urea in one portion of urine, and the ammonia 
by titration with normal sulphuric acid in another; 0.017 gram 
of ammonia = 0.030 of urea. The equivalent of ammonia in 
terms of urea must be added to the urea found in the first 
portion of urine. 

Modifications. — Rautenberg and Pfliiger have devised modifi- 
cations of Liebig's original method. Rautenberg's method 
consists in maintaining the urea solution neutral throughout by 
successive additions of calcium carbonate. Pfliiger' s method is 
as follows: A 2 per cent, solution of urea is prepared ; 10 c.c. 
of this are placed in a beaker, and 20 c.c. of the mercuric nitrate 
solution are run into it in a continuous stream ; the mixture is 
then brought under a burette containing normal sodium car- 
bonate, and this is added with constant agitation until a per- 
manent yellow color appears. The volume so used is noted as 
that necessary to neutralize the acidity produced by 20 c.c. of 
the mercurial solution in the presence of urea. A plate of glass 
is then laid on a black cloth, and some drops of a strong solu- 
tion of sodium bicarbonate (free from carbonate) are placed 
upon it at convenient distances. The mercurial solution is 
added to the urine in such volume as is judged appropriate, and 
from time to time a drop of the white mixture is placed beside 
the bicarbonate, so as to touch but not mix completely. A 
point is at last reached when the white gives place to yellow ; 
both drops are then quickly mixed with a glass rod, and the 
color disappears ; further addition of mercury is then made to 
the urine until a drop mixed with the bicarbonate remains per- 
manently yellow. Now is the time to neutralize by the addition 
of the normal sodium carbonate to near the volume found neces- 
sary in the preliminary experiment. If this is quickly done, a 
few tenths of a cubic centimeter of mercuric nitrate will be 
found sufficient to complete the reaction. If, however, much 
time has been lost, it may happen that, notwithstanding the 
mixture is distinctly acid, it gives, even after the addition of 
sodium carbonate, a permanent yellow, although no more mer- 
curic nitrate be added. Under those circumstances the analysis 
must be repeated, taking the first titration as a guide to the 
quantities that are necessary. Pflliger's correction for concen- 
tration of urea is different from Liebig's, and is as follows : 

VI = volume of urea solution -J- volume of sodium carbonate 
solution -]- volume of any other fluid free from urea that may 
be added. 

V2 r=r volume of mercuric nitrate solution used. 

C rrrr correctlon = — (VI — V2) X 0.08. 
4 



50 ORGANIC CONSTITUENTS OF NORMAL URINE. 

This formula holds good for cases in which the total mixture 
is less .than three times the volume of mercuric nitrate solution 
used ; with more concentrated solutions the formula gives results 
too high. 

Liebig's method is by far the most accurate for the quantita- 
tive determination of urea, but it is too long and complicated 
for clinical purposes. 

(b) The Hypobromite or Hypochlorite Method. — 

The principle upon which this method is based is that urea, 
when brought in contact with sodium hypobromite or 
sodium hypochlorite, is decomposed into nitrogen, carbon 
dioxide, and water. Thus : 

CH.Np + sNaOBr = 3NaBr + CO2 + Ng + 2H2O, 

the volume of nitrogen disengaged being the measure of 
the urea. The carbon dioxide set free immediately com- 
bines with the excess of sodic hydrate in the hypobromite 
mixture used, and forms sodium carbonate, which remains 
in solution. 

All qtcantitative determinations by this 7nethod are depend- 
ent upon the fact that one cubic centimeter of nitrogen gas at 
the standard temperature and pressure is eqtdvalent to o.oo2y 
gram of urea ; or, on the other Jiand, that 07ie gram of urea 
at o^ C. fu7mishes jyo c.c. of nitrogeii. 

Various forms of apparatus for the application of this 
process have been devised, among which are those of 
Hiifner, Gerrard, Dupre, W. H. Greene, Charles A. Dore- 
mus, E. R. Squibb, and others. In the use of these vari- 
ous forms only approximate results are obtained, but the 
one devised by E. R. Squibb is by far the most satisfactory 
for clinical purposes. 

SqidbUs Apparatus^ (Fig. 4). — This apparatus consists 
of two two-ounce bottles, a and b, each being supplied with 
a double-bored rubber stopper and connected by means of 
a rubber tube, c ; a 2 c.c. pipette that is closed at its 
upper end by a nipple; a 30 c.c. graduate, g, into which a 
rubber tube, d, extends from bottle b ; and a small glass 
plug, e. 



Reagents. — Among the reagents that may be used for decom- 

1 This apparatus can 
Y. , or of Messrs. Ei 
City, at a moderate cost. 



1 This apparatus can be purchased of E. R. Squibb & Sons, Brooklyn, 
N. Y., or of Messrs. Eimer & Amend, 205-211 Third Avenue, New York 



QUANTITATIVE DETERMINATION OF UREA. 51 

posing the urea in urine by this apparatus, the following are the 
most convenient and the best : 

I. The Solution of Chlorinated Soda of the United States 
Pharmacopeia of 1840 to 1870 inclusive, but the solution of 
the U. S. P. of 1880 must be avoided, as it will not answer 
the purpose. If this solution of 1870 is not accessible when this 
apparatus is to be used, it may be extemporaneously made by 
the following formula and process from the chlorinated lime 



Fig. 4.— Squibb's urea apparatus, for the approximate estimation of urea in urine. 

supplied with the apparatus, or from any other source. Fifteen 
or twenty cubic centimeters of this solution are sufficient for each 
assay. 

2. Extemporaneous Solution of Chlorinated Soda: Take of 
chlorinated lime (chloride of lime or bleaching powder) 20 
grams, or 318 grains; and sodium carbonate (common washing 
soda, or "sal soda"), 40 grams, or 636 grains. Shake the 
chlorinated lime in a bottle with 45 c.c. or i}4 fluidounces 
of water until thoroughly disintegrated. Allow the mixture 
to settle for a minute or two, and pour the thin portion 
upon a paper filter in a funnel, filtering into a bottle of about 
100 c.c. capacity. Shake the thick residue remaining in 
the bottle with 30 c.c. or i fluidounce more water, and when 
the first portion on the filter has drained through, pour the 
whole of the second portion on the filter and allow this to drain 
through. Then dissolve the sodium carbonate in 30 c.c, or i 



52 ORGANIC CONSTITUENTS OF NORMAL URINE. 

fluidounce, of hot water, and add this solution to the filtrate in 
the first bottle. Shake the solutions well, and if the mixture 
gelatinizes, warm the bottle and shake until it liquefies, and 
then pour it upon a new filter-paper, filtering off the clear solu- 
tion into a bottle marked at loo c.c. When the filtrate has 
drained through, pour water into the filter until the filtrate 
reaches the looc.c. mark on the bottle. This solution is about 
equivalent to that of the U. S. P. of 1870 for this assay, and 
when recently made, 10 c.c. of it are sufficient for each assay, but 
when old or made from old chlorinated lime, 15 c.c. are a safer 
quantity. 

3. Solution of Chlorinated Lime : Take of chlorinated lime 
(" chloride of lime ") 40 grams, or 617 grains ; water, a suffi- 
cient quantity. Shake the chlorinated lime well with 120 c.c, 
or 4 fluidounces, of water, and after the mixture has settled for 
a minute or two pour off the thinner portion on to a filter-paper, 
and filter into a bottle marked at 200 c.c, or 673 fluidounces. 
Add 80 c.c more water to the thick residue of the chlorinated 
lime, again shake well, and pour the whole upon the filter after 
the first portion has nearly all drained through. When the 
second portion has drained through, pour water on the residue 
in the filter until the filtrate reaches the 200 cc mark on the 
bottle. Then cork the bottle and shake it, label it, and date 
the label. 

For the decomposition of urea this solution is the best of all 
reagents yet tried. It is very efficient when a month old, but 
how much longer it will retain its efficiency is not known. Its 
reaction with the urea is very prompt, and is divided into two 
stages of very active reaction, which are usually from one to 
three minutes apart. Then the end reaction is fairly sharp. 
The whole time of shaking is usually not over six minutes, and 
a warm bath is not needed. Even when made from 18 per 
cent, chlorinated lime, 10 cc. of this solution are quite sufficient 
for an assay, and, therefore, the foregoing formula yields enough 
for 20 assays ; the bottle of chlorinated lime supplied with the 
apparatus contains about enough to make solution for 40 assays 
before it will need replenishing. 

4. Solution of Sodium Hypobromite : This, as applied by 
the improved process of Dr. Charles Rice, is kept in two sepa- 
rate solutions, which are mixed shortly before using them. 

(^) The solution of caustic soda is made by dissolving 100 
grams of caustic soda in 250 c.c of water, the resulting solution 
measuring about 284 cc 

(^) The solution of bromine is made by carefully weighing 
each of the following ingredients : 

Bromine I part. 

Potassium bromide I " 

Water 8 parts. 



UREA. 53 

Dissolve the potassium bromide in the water and add it to the 
bromine ; shake until the bromine is dissolved, when the solu- 
tion is ready for use. 

For the assay the bromine and the soda solutions are taken in 
equal measures, and are mixed near the time of using. AMiile 
2.5 c.c. of each solution with 5 c.c. of water, or 3.5 c.c. of each 
solution with 3 c.c. of water, are sufficient for an assay, it is 
better to take 5 c.c. of each solution for safety, and not dilute 
with water. The reaction is very prompt, and the end reaction 
is fairly definite and sharp, and there is no perceptible double 
reaction with an interval between them, as in the chlorinated 
lime solution, unless there is a larger dilution. 

Process. — i. Provide a vessel containing enough water to im- 
merse bottle a, the water being at room-temperature, — or about 
18° C. (64.4° F. ), — to be used as a cold bath. 

2. Put one end of the short rubber tube d on the bent glass 
tube of the stopper of the bottle b, and slip it on the glass tube 
just so far that when the bottle b is laid on its side on its sup- 
port, the free end of the rubber tube will just clear the bottom 
of the measuring jar, as shown in the cut. 

3. Fill the bottle b with water at room-temperature, and put 
the stopper firmly in place, allowing the displaced water to 
escape through the tubes. Then, taking the bottle in the right 
hand with the forefinger over the end of the straight glass tube 
of the stopper, incline the bottle toward the bent glass tube, 
and relax the pressure of the forefinger on the end of the 
straight tube so that water enough may escape to completely fill 
the rubber tube d. Then with the left hand put the little glass 
stopper e in the free end of d and lay bottle b, thus filled, on its 
support ; this requirement may be fulfilled by the lid of the 
box. 

4. Next, put one end of the long piece of rubber tubing (<;) 
on the bent glass tube of the stopper of the bottle a. 

5. Measure out in the graduate the quantity of the reagent to 
be used, and having poured it into bottle a, rinse out the grad- 
uate-glass. 

6. Dip the stopper of bottle a into water, and put it loosely 
in its place. 

7_. Dip the mouth of the rubber bulb of the pipette in water 
for lubrication, and put the bulb on the pipette nearly as far as it 
will go. Compress the large part of the bulb upon the pipette, 
and having dipped the point in the urine, relax the compression 
entirely. The expansion of the bulb will cause the urine to 
rise and fill — or nearly fill — the body of the pipette. Then, tak- 
ing the body of the pipette between the left thumb and fingers 
while the point is still immersed in the urine, with the right 
thumb and forefinger applied to the rubber ring at the mouth of 



54 ORGANIC CONSTITUENTS OF NORMAL URINE. 

the bulb, screw the bulb upward on the pipette so that the urine 
may slowly rise to the mark until the lower limb of the menis- 
cus lies just above the mark. Now, when the point of the pipette 
is raised out of the urine, the meniscus will fall a little, and lie 
exactly on the mark. Then screw the bulb a little higher, so 
that a very little air may enter the point of the pipette, to prevent 
loss of the measured urine. 

8. Pass the lower end of the charged pipette through the 
vacant hole in the stopper of bottle a, and then screw the stop- 
per into its place by holding the stopper firmly, and turning the 
bottle upon it. 

9. Then put the free end of the long rubber tube c on the 
end of the straight glass tube of the stopper of bottle b, thus 
connecting a and ^. 

10. Next, take out the little glass stopper e from the free 
end of the short rubber tube d, and allow the few drops of water 
that will flow to escape, seeing that the flow ceases completely. 

11. Then put the empty measuring jar in its place under the 
tube d, to receive the displaced water of the process, when the 
preparation for the process will be complete. 

12. Take the bottle a by the neck, between the right thumb 
and forefinger, and take the upper part of the pipette with the 
left thumb and fingers, in readiness to compress the rubber bulb, 
shaking the lower part of the bottle from side to side, and not 
up and down. During this gentle shaking compress the bulb, 
so as to force all the urine out of the pipette into the bottle 
with the reagent. Active effervescence will soon commence, 
and while it is active relax the compression of the bulb gradu- 
ally and completely. If this be properly done, no liquid — or 
but a drop or two — will get into the rubber tube to be carried 
over into bottle d. Continue the shaking as long as bubbles of 
gas pass over into bottle b. If chlorinated soda solution be 
used as the reagent and without a warm bath, the shaking will 
require from twenty to thirty minutes ; but with the warm bath, 
not more than from six to eight minutes. 

13. Bottle a is then immersed in the cold bath, at about 18° 
C. (64.4° F.), for about four minutes. During this immersion 
the contraction in bottle a will draw water from bottle b into a 
and from the measuring jar back into bottle b, and when there 
is no longer any change in the measuring jar, the contraction is 
finished. 

14. The bottles are removed and set aside to be prepared 
for a new assay ; and the contents of the measuring jar are 
carefully read off to half a cubic centimeter, and the quantity 
thus obtained is noted and referred to the first column of the 
urea table. There the proportion of urea present is found 
calculated in percentage, and in grams and grains for various 



UREA. 



55 



TABLE OF APPROXIMATE PROPORTIONS OF UREA IN 
URINE, FOR CLINICAL USE. 

One cubic centimeter of nitrogen gas at o° C. (32° F.) equals 0,0027 gram 
of urea. 

Assumed room- temperature for measurements, 18° C. (64.4° F.). 

Rate of expansion, 0.003663 times the volume for each I°C. Correction 
apphed for 18° C. (64.4° F.) is 0.003663 x 18 =0.0659 subtracted for each 
I c.c. as read off from the measuring jar, and the percentage is calculated from 
the corrected reading. 

Thirty cubic centimeters are assumed as equal to one fluidounce, but in con- 
verting any considerable quantities from one measure to the other 29.52 c.c. 
should be taken as one fluidounce. 

In converting measures to weights, and in using measures and weights to- 
gether, an assumed specific gravity for abnormal urine is taken — namely, 1025 
at 25° C. (77° F. ) ; and 30 c.c. of urine of such specific gravity weigh 30.75 
grams, and one fluidounce weighs 467.4 grains. 

Four hundred and seventy-three cubic centimeters are assumed as equal to 
one pint, or sixteen fluidounces, and when these measures are used for urine, 
they are assumed as weighing 484.83 grams (1025 x 473) and 7478.4 grains 
(467.4 X 16) respectively. 

The seventh and eighth columns must not be taken as having any definite 
relation to, or bearing upon, the assay, excepting when the total twenty-four- 
hour excretion amounts to just 1 181 c.c, or 40 fluidounces, or very near to this 
measure, as the calculations are based upon this arbitrary quantity. 





to 


Urea Con- 


Urea Con- 


Urea Con- 


Hi2 




. 


tained IN 30 
c.c, or I Fluid- 


tained IN 473 
C.C, OR I Pint, 


tained IN 1 181 
CO., OR 40 


CoNSIS 

thOrd 

EALTH 
ULTS. 
BABLE.) 


OZOH 

OS ^ w 


^f\ 


ounce, of 


OF Urine. 


Fluidounces, 


ss 


Urine. 




OF Urine. 


Z 3 Z k; 


WD 

u 

0!: 










Limits 

ENT wi 
NARY H 

Ad 
(Pro: 


Reaui 

Meas 

(Cor 


In 


In 


In 


In 


In 


In 


Oh 


Grams. 


Grains. 


Grams. 


Grains. 


Grams. 


Grains. 


4 c.c. 


0.50 


0.1538 


2.34 


2.425 


37.44 


6.055 


93.60 




s " 


0.63 


0.1937 


2.94 


3.054 


47.04 


7.625 


117.60 


. . . 


6 " 


0.76 


0.2337 


3.55 


3.685 


56.80 


9.200 


142.00 


. . . 


7 " 


0.88 


0.2706 


4.11 


4.267 


65.76 


10.653 


164.40 . 


. . . 


8 " 


I.OI 


0.3106 


4.72 


4.897 


75.52 


12.227 


188.80 


. . . 


9 " 


I-I3 


0.3475 


5.28 


5.479 


84.48 


13.680 


211.20 


. . . 


10 " 


1.26 


0.3875 


5.89 


6.1X0 


94.24 


15255 


235.60 




II " 


1-39 


0.4274 


6.50 


6.739 


104.00 


16.825 


260.00 


. . . 


12 " 


I-5I 


0.4643 


7.06 


7.321 


112.96 


18.278 


282.40 




13 " 


1.64 


0.5043 


7.67 


7951 


122.72 


19.853 


306.80 


Lowest. 


14 " 


1.77 


0.5443 


8.27 


8.582 


132.32 


21.427 


33080 




15 " 


1.89 


0.5812 


8.83 


9.164 


141.28 


22.880 


353-20 


. . . 


16 " 


2.02 


0.6212 


9.44 


9.794 


151.04 


24.455 


377.60 




17 " 


2.14 


0.6581 


10.00 


10.376 


160.00 


25.907 


400.00 




18 " 


2.27 


0.6980 


10.61 


11.005 


169.76 


27.478 


424.40 




19 -" 


2.40 


0.7380 


11.22 


11.636 




29.053 


448.80 




20 " 


2.52 


0.7749 


11.78 


12.218 


18848 


30.505 


471.20 


Normal. 


21 " 


2.65 


0.8149 


12.39 


12.849 


198.24 


32.080 


495.60 


. . . 


22 " 


2.77 


0.8518 


12.95 


13.430 


207.20 


33-533 


518.00 




23 " 


2.90 


0.8918 


13.55 


14.061 


216.80 


35.107 


542.00 


. . . 


24 " 


3-03 


0.9317 


14.16 


14.690 


226.56 


36.678 


566.40 


. . . 


25 " 


3-15 


0.9686 


14.72 


15.272 


235.52 


38.131 


588.80 


. . . 


26 " 


3.28 


1.0086 


15.33 


15.903 


245.28 


39.706 


613.20 


. . . 


27 " 


340 


1.0455 


15.89 


16.484 


254.24 


41.158 


635.60 


Highest. 



56 ORGANIC CONSTITUENTS OF NORMAL URINE. 

measures of urine. For example, if the graduate -glass contains 
1 6 c.c. of displaced water, from the urea table it will be found 
that the urine contains 2.02 percent, of urea, or 0.6212 grams in 
30 c.c. of urine, {a) If the twenty-four-hour quantity of urine be 

1 500 c. c. , then calculating from the percentage — — ^^ — = 30-30 

grams, which represents the approximate number of grams of 
urea in twenty-four hours. {I') Or, calculating from the third 

1 -1.11 O.62I2Xl'50O , r 1 . T 

column in the table, —31.05 grams, which represents 

the accurate number of grams of urea in twenty-four hours. 

Joslin ^ has recently pointed out that in severe cases of 
diabetes mellitus the amount of urea obtained by the use of 
Squibb's apparatus for urea (Hypobromite Method) is in- 
variably too high ; that either the acetone, /5-oxybutyric 
acid or ammonia present in the urine has an action similar 
to urea. He recommends the use of Braunstein's method ^ 
in such cases. 

Doremus Ureometer. — The apparatus as represented in 
figure 5 was devised by Dr. Charles A. Doremus, of New 
York. It is much used for rapid clinical purposes, and 
consists of a bulb with an upright graduated tube, and a 
small nipple-pipette to hold one cubic centimeter of urine. 
The tube is so graduated that each of the small divisions 
represents 0.00 1 gram of urea. The bulb is filled with 
the sodium hypobromite solution, and the apparatus in- 
clined sufficiently to fill the upright graduated tube, and 
then water is added to fill the remainder of the tube and 
lower part of the bulb. The pipette is filled with urine to 
the one cubic centimeter mark, and the point carefully in- 
troduced into the bend as far as it will go, holding the 
graduated tube perpendicularly. The nipple is then slowly 
compressed to expel all of the urine, care being taken not 
to force air into the tube after the urine has been expelled. 
The pipette is then withdrawn, and after the evolution of gas 
is complete the number of cubic centimeters of nitrogen 
gas is read off, and the result multiplied by 100 in order to 
obtain the percentage of urea. Two forms of this apparatus 
are obtainable — one graduated to read fractions of a gram 
per cubic centimeter of urine, and the other graduated to 
read the number of grains of urea per fluidounce of urine. 

1 "Journal of Medical Research," vol. vi, Nov., 1901. 

2 " Hoppe-Seyler's Zeitschr. f. physiol. Chemie," 1900, xxxi. 



UREA. 



57 



The Doremiis tireometcr as modified by Professor J. D. 
Hinds (Fig. 6) has many advantages over the original form 
of apparatus. This instrument consists of a bulb with an 
upright graduated tube {a), the same as the original ; near 
the lower portion of this tube is a horizontal glass connec- 




r^ 




Fig. 5. — Doremus ureometer. 



Fig. 6. — Hinds' modification of the Dore- 
mus ureometer. 



tion, which is provided with a ground glass stop-cock {p)y 
and which supports another upright graduated tube (<r) 
with a capacity of two cubic centimeters. The bulb and 
upright tube (a) are filled with the sodium hypobromite solu- 
tion in precisely the same manner as previously described. 
The upright tube {c) is then filled to the zero mark with 
the urine to be tested. The stop-cock (B) is then turned, 
and exactly one cubic centimeter of the urine allowed to 
enter tube a with the reagent. As soon as the evolution 
of nitrogen gas is complete, the number of cubic centi- 
meters of the gas is read off, and the result multiplied by 
100 in order to obtain the percentage of urea. 

This form of apparatus ^ gives more exact results than the 

1 This instrument, as well as the original Doremus ureometer, can be ob- 
tained at a moderate cost from Messrs. Eimer & Amend, 205 to 211 Third 
Ave., New York City. 



58 ORGANIC CONSTITUENTS OF NORMAL URINE. 

original form, since the one cubic centimeter of urine re- 
quired for the test is delivered with greater accuracy, and 
no nitrogen gas is lost by its escape from the bulb. 

(c) Morner-Sjoqvist Method. — By the use of this 
method all of the nitrogenous constituents of the urine, 
except the urea and ammonia, are precipitated by means 
of alcohol and ether after the addition of a solution of 
barium chloride and barium hydrate; and finally the urea 
is determined in the concentrated filtrate, after driving 
off the ammonia, by Kjeldahl's Nitrogen Method. 

Process. — Place 5 c.c. of the urine in a flask ; add 5 c.c. 
of a saturated solution of barium chloride which contains 5 
per cent, of barium hydrate ; to this add 100 c.c. of a 
mixture of two parts of alcohol (97 per cent.) and one part 
of ether and allow it to stand in the closed flask for twelve 
hours. The precipitate is then filtered off and washed with 
alcohol and ether. The alcohol and ether are removed 
from the filtrate by distillation at about 55° C. When the 
fluid has become concentrated to about 25 c.c. add a little 
water and some calcined magnesia. Continue the evapora- 
tion down to 10 or 15 c.c, or until the vapors are no longer 
alkaline in reaction. Transfer the liquid to a flask by the 
aid of a little water, treat with a few drops of concentrated 
H2SO^, and further concentrate on the water-bath. In this 
concentrated liquid the total nitrogen is determined accord- 
ing to the method of Kjeldahl. (See below.) 

The quantitative estimation of urea should be accompanied 
by a determination of the total nitrogen in the diet, feces, 
and urine, in order to be able to draw intelligent inferences 
regarding excretion. 



KJELDAHUS TOTAL NITROGEN DETERMINATION, 

This method consists in converting all the nitrogen of 
organic compounds into ammonia by the use of concen- 
trated sulphuric acid and heat. The ammonia is distilled 
over and collected in standard sulphuric acid. 

Process. — Take exactly 5 c.c. of the filtered urine ; place in 
a long-necked Kjeldahl digestion flask, add a drop of metallic 
mercury, and then treat with from 10 to 20 c.c. of strong sul- 
phuric acid. Adjust the flask obliquely over a gas-flame, and 
heat gently until the vigorous action has ceased ; then gradually 



URIC ACID. 59 

increase the heat until the mixture boils. After boiling for about 
fifteen minutes, add lo grams of potassium sulphate and continue 
the boiling until the contents of the flask are clear and colorless. 
On cooling, wash the contents of the flask into a spacious dis- 
tilling flask, thoroughly rinsing the digestion flask with water. 
Place some zinc shavings in the distilling flask to prevent bump- 
ing, and then add an excess of a 30 to 40 per cent, solution of 
caustic soda which is free from nitrates and which has previously 
been treated with 30 to 40 c.c. of a 4 per cent, solution of 
potassium sulphide. Quickly connect the flask with the con- 
denser tube, and distil off all the ammonia, which is collected in 
a measured amount (not less than 25 c.c.) of — sulphuric acid. 
In order to prevent loss of ammonia, the end of the exit tube 
should be below the surface of the standard acid ; a bulb blown 
on the exit tube will prevent the regurgitation of the acid. 

When the distillation is completed, the standard acid solution 
that has been used is titrated with — caustic soda, using litmus, 
cochineal, methyl -orange, rosolicacid, or lacmoid as an indicator. 
Each cubic centimeter of the — sulphuric acid corresponds to 2 . 8 
milligrams of nitrogen. 

It is, of course, essential that the reagents employed should 
be practically free from nitrogen, but it is desirable to make a 
blank experiment from time to time in order to ascertain the 
correction to be made for the unavoidable traces of nitrogen 
that may be present. 

The use of mercury or its oxide hastens the destruction of 
the organic matter, and therefore shortens the time of digestion, 
which is rarely more than one hour. Potassium sulphide is used 
to remove all mercury from the solution, and thus prevent the 
fomiation of mercuro -ammonium compounds, which are not 
completely decomposed by the caustic soda. The addition of 
the zinc gives rise to the evolution of hydrogen and prevents 
violent bumping. 



URIC ACID. 

C5H4N4O3. 

Uric acid (H2U, expressed also U) is, in mammals, next 
to urea, the medium by which the largest quantity of nitro- 
gen is excreted from the body. It is, however, in birds 
and reptiles the principal nitrogenous constituent of the 
urine. 

Until recently, the theory of the formation of uric acid 
was that it was a product of the metabolism of the nitro- 
genous material ingested, and that it represented an inter- 



60 ORGANIC CONSTITUENTS OF NORMAL URINE. 

mediate product between the nitrogenous substances and 
the final product, urea. The researches of Horbaczewski, ^ 
Hopkins and Hope,^ Jerome,^ and others tend to show 
that uric acid has an entirely different origin. It is now 
believed that uric acid is at least partly derived from the 
nucleins that form a constituent of all cell-nuclei, and which 
are taken into the body as food. The nucleins are capable 
of being split up into an albumin and nucleic acid, and it is 
thought that the uric acid is formed in the body from the 
nucleic acid through the oxidation of the xanthin or alloxur 
groups contained in a molecule of nucleic acid. It has 
been demonstrated that the ingestion of food that is rich in 
nucleins results in the formation and elimination of a much 
larger quantity of uric acid than the ingestion of an equal 
amount of food that is poor in nucleins. The chief evi- 
dence, however, in favor of the view that nucleins play a 
role as precursors of uric acid is based upon the results of 
thymus feeding. The experiments of Hopkins and Hope, 
however, show that extracts of the thymus gland may be 
prepared which contain only traces of nucleins and nucleic 
acid, but which, when ingested, produce the characteristic- 
ally large excretion of uric acid. It, therefore, appears 
that some more soluble constituent of the diet acts either 
as a direct precursor, or as a factor in the formation of 
uric acid. 

Our knowledge of this subject is yet too meager to war- 
rant the conclusion that this new theory fully explains the 
formation of uric acid, but there can be no doubt that the 
nucleins (nucleic acid) play an important part in its forma- 
tion. 

When uric acid is referred to as a constituent of normal 
urine, it is never to its free state that allusion is made, but 
to its combinations chiefly with potassium, sodium, and 
ammonium, and also with calcium and magnesium ; such 
combinations being usually known as mixed urates. 

Under ordinar}^ conditions uric acid exists in the urine in 
the form of urates. Since uric acid is dibasic, — that is, has 
two replaceable atoms of hydrogen, — two forms of salts 
exist — i. e., acid urates of potassium, sodium, and ammo- 
nium, in which only one atom of the hydrogen is replaced 

1 "Monatsh. f. Chem.," S. 624, 1889. 2 " journ. of Physiol.," xxiil, p. 271. 
3"Journ of Physiol.," XXII, p. 146. 



URIC ACID. 61 

by the positive elements or radicles ; and normal (neutral) 
salts of the same substances, in which both atoms of hydro- 
gen are replaced. According to Neubauer and Vogel, 
there are two forms of acid urates — monacid urates (bi- 
urate), and triacid urates (quadriurate or tetraurate). The 
normal salts are readily soluble in water at 70° F., but the 
acid urates are only feebly soluble, while uric acid itself is 
almost insoluble in water. Hence, the precipitation of the 
acid urates or uric acid often occurs when the urine cools, 
or is allowed to stand in a cold place. A urine containing 
a deposit of acid urates (amorphous urates) is usually more 
or less concentrated, and always contains a relative excess 
of the acid urates. If a strong acid be added to a urine 
that contains a relative excess of urates, they are precipi- 
tated on account of the feeble solubility of the acid urates 
and the almost insoluble uric acid. Also, if the urine con- 
tains an excess of normal urates, they are partially decom- 
posed by the acid, which chemically unites with the excess 
of the base to form acid urates, hence their precipitation. 
Thus, in the nitric-acid test for albumin (performed accord- 
ing to instructions given on p. 124) a white zone of acid 
urates is frequently seen above the zone of albumin (Fig. 
1 5), or above where the zone of albumin would be if pres- 
ent. It should be borne in mind that a zone of urates may 
be present when albumin is absent. 

Pure uric acid is soluble in 16,000 parts of cold water 
and in 1600 parts of boiling water; impure uric acid is 
more readily soluble in water than the pure. Its cold solu- 
tions do not show an acid reaction with litmus paper. Uric 
acid is insoluble in alcohol and ether, but dissolves in warm 
glycerin, from which, on cooling, it separates in crystalline 
form. It is insoluble in strong mineral acids, but is soluble 
in alkaline hydrates as well as in alkaline carbonates, phos- 
phates, lactates, and acetates. It is more soluble in solu- 
tions of urea than in water (Riidel). 

On boiling, uric acid reduces alkaline solutions of copper ; 
before reduction occurs, however, a white precipitate, con- 
sisting of cuprous urate, is formed. 

When uric acid is artificially decomposed, an interesting 
series of products results, the most important of which is 
urea. Whether similar changes take place in the body is 
still a matter of doubt. 



62 ORGANIC CONSTITUENTS OF NORMAL URINE. 

The following is a list of the principal changes which 
may be brought about by various reagents : 

1. When uric acid is reduced with weak sodium amalgam, 
two substances — xanthin (C5H^N^02) and hypoxanthin or sar- 
kin (C.H^N^O) — may be obtained. Their formulas differ from 
that of uric acid in containing one or two atoms less oxygen re- 
spectively than that substance. 

2. When uric acid is heated in a closed tube with hydro- 
chloric acid, it is decomposed into glycocoll, carbonic acid, and 
ammonia : 

QH.NA + 5H2O = C^H.NO, + 3CO2 + 3NH3. 

3. By the action of cold, concentrated nitric acid or lead di- 
oxide, uric acid takes up water and oxygen, forming alloxan 
and urea : 

2C5H^N,03 + 2H2O + 02 = 2C,H2N20, -f 2CON2H,. 
Uric acid. Alloxan. Urea. 

2C^H2N20^ -b O2 = 2C3H2N2O3 + 2CO2. 
Alloxan. Parabanic acid. 

C3H2N2O3 -f HjO = CgH^NjO,. By boiling = 
Oxaluric acid. 

C3H,N20^ -f H2O = H2C2O, + CH,N20. 
Oxalic acid. Urea. 

Alloxan, when boiled with a strong alkali, takes up water and 
is decomposed, forming mesoxalic acid and urea : 

2C^H2N20, -f 4H2O = 2C3H2O5 +»2CON2H4. 

Alloxan. Mesoxalic Urea, 

acid. 

On oxidation, mesoxalic acid forms oxalic and carbonic acids : 
2C3H2O5 + 02 = 2C2H2O, + 2CO2. 

Thus, it is seen that in three steps the ultimate products of uric 
acid are urea, oxalic acid, and carbonic acid. 

4. There is another way in which the same three ultimate 
products are obtained, but the intermediate step in the process 
is not the formation of alloxan, but of another somewhat similar 
substance called allantoin. This process is interesting, as allan- 
toin is in fetal life one of the products of nitrogenous metabol- 
ism, and it is thus possible that some sort of change, such as 
can be produced artificially, occurs in embryonic life. 

Uric acid when oxidized with potassium permanganate (care 



URIC ACID. 63 

being taken that the temperature does not rise) takes up water 
and oxygen, forming allantoin and carbonic acid : 

2C5H,N,03 + 2H2O + 0,= 2C,HeNp3 + 2CO,. 

Uric acid. Allantoin. 

The allantoin crystallizes out in about twenty-four hours. By 
subjecting allantoin to the action of baryta water, hydrolysis 
and oxidation again take place, and urea and oxalic acid are 
formed : 

2C,H6N,03 + 4H2O + O2 = 4CON2H, + 2C,U,0,. 

Allantoin. Urea. Oxalic acid. 

5. The following decompositions are interesting, as the 
murexide test is the chief characteristic test for uric acid. 

By oxidation with nitric acid, alloxan and urea are formed : 

2C5H,N,03-h2H20+02 == 2C,H2N20, + 2CON2H,. 

By heating or by electrolysis, alloxan splits into alloxantin, 
parabanic acid, and carbonic acid : 

SC.H^KA = CgH.N.O, + C3H2N2O3 + CO2 ; 
Alloxan. Alloxantin. Parabanic 

acid. 

and on treating alloxantin with ammonia the purple color due 
to murexide or purpurate of ammonia appears : 

CgH^N.O, + 2NH3 = C,U,-Np, + up. 

Alloxantin. Murexide. 

Since uric acid exists in combination as urates, it is not 
ordinarily found in a free state. It may, however, be de- 
posited in the urine in crystalline form, either while in the 
body or after the urine has been voided. It may then be 
seen as a deposit of minute reddish crystals, or, more 
rarely, as reddish sand or gravel. 

Uric acid crystallizes in the form of yellow or yellowish- 
red crystals of a variety of shapes — rhombic and rectangular 
prisms, whetstone-, barrel-, wedge-, club-, diamond-shaped, 
and as rosettes. (Plate 3.) The diamond-shaped crystals 
usually either have a very faint yellow tint or are, not in- 
frequently, perfectly colorless. 

Crystals of uric acid and those of its salt, — ammonium 
urate, — together with those of hippuric acid and leucin, 
constitute the only crystalline sediments of the urine col- 
ored yellow or yellowish-red. 

There are certain conditions of the body in which, as a 
result of overfeeding and consequent sedentary habits, and 
in some cases from hereditary influences, the oxidation 



64 ORGANIC CONSTITUENTS OF NORMAL URINE. 

changes in the body are lessened, and uric and oxaHc acids 
are formed in greater proportion to urea than under normal 
conditions. 

Where is Uric Acid Formed? — Two different views upon 
this subject have been advanced : (i) That it is formed in the 
tissues, especially in the liver and spleen, and merely ex- 
creted by the kidneys ; (2) that the kidneys not only excrete, 
but also constitute the seat of formation of, uric acid. The 
former view (i) is most generally held, and is supported by 
the following facts : (a) Under normal conditions uric acid 
is found in traces in the blood, (d) After extirpation of 
the kidneys it continues to be formed, {c) The secretion 




Fig. 7. — Uric acid and urates (Funke). 

of uric acid is greatest during the period of digestion- — that 
is, at a time when the liver and spleen are most active, (d) 
In gout and in anemic conditions, ^ where the excretion of 
uric acid is diminished, it accumulates in the blood and tissues. 

The chief advocate of the second view (2) is Garrod, who 
bases his conclusions on the fact of the small amount of uric 
acid in the blood of reptiles, and also on the fact that he 
was unable to find a larger quantity of uric acid in the 
liver and spleen of birds than in those organs in mammals. 

Horbaczewski ^ claims that uric acid is formed as a re- 
sult of the disintegration of the tissues containing nuclein, 

1 Von Jaksch, " Deutsche med. Wochenschr.," 1890, No. 23. 

2 *' Monatsh. f. Chemie," Bd. xii, 232, 1891. 



Plate 3 




Uric-acid Crystals; Normal Color (after Peyer). 



URIC ACID. 65 

especially the leucocytes ; that the amount of uric acid 
excreted increases when the number of leucocytes in the 
blood is increased. He also claims that this is the explana- 
tion of the large amount of uric acid in the urine of chil- 
dren, especially the new-born, the small amount in hunger, 
and the larger quantity following the ingestion of a meat diet. 

The investigations of Schroder^ and Minkowski^ justify 
the conclusion that uric acid is formed chiefly in the liver, 
where it appears as a result of the synthesis of ammonia 
and lactic acid, which, after the removal of the liver, and 
also in extensive degenerative changes of this organ (cirrho- 
sis, acute yellow atrophy, etc.), appear in the urine in equiv- 
alent quantities. Further, that small quantities of uric acid 
following extirpation of the liver are formed from xanthin 
and similar substances. 

The quantity of uric acid eliminated in twenty-four hours 
under normal conditions ranges between 0.2 and i gram, the 
average being about o. 5 gram. According to Neubauer and 
Vogel,^ the twenty-four-hour quantity may, normally, go as 
high as 1.25 grams. In rare instances, especially in disease, 
the total quantity of uric acid may exceed this figure. The 
proportion of uric acid to urea is normally about as i : 45. 

The quantity of uric acid in the urine is not necessarily 
excessive w^hen a deposit of uric acid crystals takes place 
in the urine upon cooling. As a matter of fact, such a de- 
posit may, and very often does, occur when the quantity 
of uric acid is both relatively and absolutely diminished. 
The separation of uric acid crystals from the urine is 
usually dependent upon one of three conditions : 

1. A high degree of concentration of the urine, too 
little water being present to keep the uric acid in solution. 

2. Marked acidity of the urine, the salts of uric acid 
being deprived of a part of the alkali ; the larger the pro- 
portion of alkali combined with the uric acid, the more 
soluble it becomes. 

3. A high percentage of uric acid. Any condition 
that results in an increased formation of uric acid in the 
body causes its increase in the blood, and hence an 
increased amount in the urine, with, usually, a resulting 
deposition of the crystals. 

When urine habitually contains a deposit of uric acid, an 

1 '<Ludwig's Festschrift," 1887, S. 89. "^Loc. cit. 

3 ''Analyse des Harns," Bd. i, 1898, S. 312. 
5 



66 ORGANIC CONSTITUENTS OF NORMAL URINE. 

alkali or some substance with which the uric acid will com- 
bine should be administered, in order to prevent an irrita- 
tion or inflammation of the urinan,^ tract by the crystals. 

In the consideration which follows the writer refers to the 
uric acid in solution (as urates) and not to a deposit of uric 
acid crystals. 

Clinical Significance. — Uric acid is absolutely in- 
creased (i) by an abundant nucleo-proteid diet, especially 
when combined with a limited amount of outdoor exercise : 
in other words, increased metabolism together with limited 
oxidation. (2) In most of the acute diseases. (3) In 
acute diseases of the lung, as in pneumonia, or by any dis- 
ease that interferes with respiration, as hydrothorax and 
pneumothorax, also by the upward pressure of abdominal 
tumors, marked ascites, etc. (4) In chronic heart disease 
or in any condition that interferes with the circulation. (5) 
In liver disease. (6) In disease of the spleen. (7) In vari- 
ous forms of anemia, especially splenic leukemia, in which 
case the proportion of uric acid to urea may be as high as 
I : 15, or even more. (8) In gout following the par- 
oxysm, (9) In diabetes mellitus.^ (10) Following the 
administration of nuclein. ^ 

Uric acid is absolutely diminished (i) by a diet low 
in nucleo-proteids. (2) By the habitual ingestion of large 
quantities of water (long-continued use). (3) In most forms 
of advanced disease of the kidneys. (4) In gout during the 
paroxysm. (5) Following the administration of large 
doses of quinine. (6) In most oi the general chronic dis- 
eases. 

Detection. — i. The Murexide Test. — A small portion 
of urinary sediment is evaporated to drj'ness on a porcelain 
plate or capsule, and a drop or two of nitric acid is added to 
dissolve it. The mixture is then stirred thoroughly with 
a glass rod, and carefully evaporated to dryness over a 
spirit or a small Bunsen flame. When dry and cool, add 
one or two drops of ammonic hydrate, and if uric acid 
or urates are present, a beautiful purple-red color promptly 
appears, gradually diffusing itself over the bottom of the 
plate or capsule as the ammonia spreads. 

^ The question as to whether uric acid is actually increased in diabetes 
mellitus has given rise to much controversy. It is probable that the increase, 
if any, is not marked. 

2 <' Monatsh. f. Chemie," Bd. xii, 234, 1891. 



URIC ACID. G7 

2. Strongly acidulate the urine with concentrated hydro- 
chloric acid, and allow the mixture to stand from eighteen 
to twenty-four hours. Usually, a deposit of uric acid crys- 
tals appears. 

3. Uric acid may be detected in the urine and other 
fluids, when traces of the acid or of urates are present, by 
a method suggested by Garrod. A small portion of the 
suspected fluid is treated on a watch-glass with a few drops 
of glacial acetic acid. A few filaments of tow or very thin 
silk are placed in the mixture, and the whole is set aside 
under a bell-jar in a warm place for from twenty-four 
to forty -eight hours. Gradually, crystals of uric acid sepa- 
rate and are deposited upon the filaments. Their character 
may be readily recognized by microscopic examination. 

4. When a solution of uric acid or of a urate is boiled 
with an alkaline solution of copper (Fehling's solution), a 
yellowish-red or reddish precipitate of suboxide of copper 
occurs. 

Quantitative Determination of Uric Acid. — Heintz's 
Method. — Take 200 c.c. oi filtci^cd \ix\x\q that is free from 
albumin, and add 10 c.c. of concentrated hydrochloric acid. 
Let this stand for twenty-four hours in a cool place, then 
collect the separated uric acid crystals on a previously dried 
and weighed filter-paper, and wash once or twice with cold 
distilled water. Dry the filter-paper holding the uric acid 
crystals at about 100° C.; cool and weigh. By subtracting 
the weight of the filter-paper, the result will be the weight 
of the uric acid in 200 c.c. of urine. 

This process can be considered only approximate, and 
should not be relied upon for accurate results. It fre- 
quently happens that urines containing uric acid do not 
give a precipitate by this method ; it then becomes neces- 
sary to employ other longer and, probably, more accurate 
methods. 

Salkcwski-Ludwig Method. ^ — Of the several gravi- 
metric methods which have been suggested, this is perhaps 
the most reliable. It consists in separating the uric acid 
from the urine by means of magnesia mixture and silver 
nitrate, and weighing the uric acid obtained from the silver 
precipitate. 

1 Salkowski, "Virchow's Archiv," Bd. Lii, 1871, S. 58; "Pfliiger's 
Archiv," Bd. v, 1872, S. 210. E. Ludwig, " Wiener med. Jahrbuch," 1884, 
S. 597; "Zeitschr. f. analyt. Chemie," 24, 1885, S. 637. 



68 ORGANIC CONSTITUENTS OF NORMAL URINE. 

Process. — Place from lOO to 200 c.c. of the filtered urine, 
freed from albumin (see p. 131), in a beaker. In another 
beaker mix 10 to 20 c.c. of an ammoniacal solution of silver ^ 
with 10 to 20 c.c. of magnesia mixture (see foot-note, 
p. 109), and add ammonia, and also, when necessary, some 
ammonium chloride, until the mixture is clear. Add this 
mixture to the urine, stir thoroughly, and allow to stand 
for half an hour. Collect the precipitate on a filter paper, 
wash with ammoniacal water, and then return the precipi- 
tate to the same beaker by means of a glass rod and a wash- 
bottle, without destroying the filter. Next heat 10 to 
20 c.c. of the sodium sulphide solution, ^ which has been 
previously diluted with water, and allow it to flow through 
the filter that has already been used, into the beaker con- 
taining the silver precipitate, and wash with boiling water; 
then heat the contents of the beaker over a water-bath for 
a few minutes, constantly stirring. Cool, filter into a por- 
celain dish, wash with boiling water, acidulate the filtrate 
with hydrochloric acid, evaporate to about 15 c.c, add a 
little more hydrochloric acid, and finally allow it to stand 
(preferably in an ice-chest) for from eighteen to twenty-four 
hours. Collect the crystallized uric acid on a previously 
dried and weighed filter paper ; wash with a small amount 
of water, then with alcohol, ether, and carbon disulphide ; 
dry in an oven at 100° to 110° C, and weigh. 

Corrections and Precantions. — (i) For each 10 c.c. of 
watery filtrate add 0.00048 gram to the final quantity of 
uric acid obtained. (2) A portion of the uric acid may be 
decomposed if heated too long or too vigorously with the 
sodium sulphide solution. 

Hopkin's Method. — In this process the uric acid and 
all of the urates are precipitated by saturating the urine 
with ammonium chloride, which converts all into am- 
monium urate. This is then filtered out, and the uric 
acid separated by the action of hydrochloric acid. The 
final estimation is then made by titrating with a standard 
solution of potassium permanganate, which Hopkins has 
found to be more accurate than weighing. Exceedingly 

1 Silver nitrate 26 grams, distilled water ad. i liter ; add sufficient ammonic 
hydrate to completely redissolve the precipitate produced by the first addition 
of the ammonia. 

2 Caustic soda (free from nitric and nitrous acids) 10 grams, distilled water 
J liter. Completely saturate one-half of this solution with sulphuretted hy- 
drogen, and then add it to the other half. 



URIC ACID. 69 

accurate results are claimed for this process, and it has 
the advantage of being conducted with ease and compara- 
ti\^e rapidity. 

The following solution is required : A twentieth-normal 
solution of potassium permanganate. This solution is pre- 
pared by dissolving 1.577 grams of pure crystals of potas- 
sium permanganate in about 900 c.c. of distilled water. A 
portion of this solution is then placed in a burette and 
titrated against a decinormal solution of oxalic acid as fol- 
lows : Take 10 c.c. of the decinormal oxahc acid solution 
in a beaker, add some dilute sulphuric acid, and heat this 
mixture to 60° C. To this hot mixture add the solution 
of potassium permanganate until a faint but permanent pink 
color is produced. Note the number of cubic centimeters 
of the permanganate solution used, and then dilute the 
remainder so that 20 c.c. of it will exactly correspond to 
10 c.c. of the decinormal solution of oxalic acid. 

Each cubic centimeter of the twentieth-normal solution 
of potassium permanganate corresponds to 0.00375 gram of 
uric acid. 

The permanganate solution will usually retain its strength 
for several weeks, but it should always be restandardized 
by titration with oxalic acid before it is used. 

The process, as applied to all urines, normal and patho- 
logic, is as follows : 

I. In Normal Urine without Deposit. — {a) To 100 c.c. 
of the urine is added ammonium chloride until practically 
saturated ; about 3 5 grams are necessary. When a small 
quantity of the chloride remains undissolved, even after 
brisk stirring at intervals of a few minutes, saturation 
is nearly complete. As the temperature of the urine again 
rises, from the depression due to the process of solution, 
any residual crystals will, for the most part, dissolve ; but 
there is no necessity for adding more. 

ib) After having stood for two hours or longer, — better 
with occasional agitation to promote subsidence, — the pre- 
cipitate produced is filtered through a thin filter-paper, 
and washed three or four times with a saturated solution 
of ammonium chloride. The filtrate should remain per- 
fectly clear. 

if) With a jet of hot distilled water the urate, which 
will be somewhat pigmented, is now washed off the filter 



70 ORGANIC CONSTITUENTS OF NORMAL URINE. 

into a small beaker, and heated just to boiling with an 
excess of hydrochloric acid. It is then allowed to stand, 
in order that the uric acid may separate completely. Two 
hours are sufficient if the liquid be cooled. The acid is 
then filtered off and washed with cold distilled water. The 
filtrate should be measured before the washing is begun, 
and one milligram added to the final result for each 15 c.c. 
of liquid present. This need never be more than from 20 
to 30 c.c. 

(d') The acid is now again washed off the filter with hot 
water, sodium carbonate is added, it is warmed until dis- 
solved, and the solution then made up to 100 c.c. Being 
transferred to a flask of sufficient capacity, it is mixed with 
20 c.c. of concentrated pure sulphuric acid, and immediately 
titrated with the twentieth-normal potassium permanganate 
solution. The latter should be added slowly toward the 
end of the reaction, the close of which is marked by the first 
approach of a pink color, which is permanent for an appre- 
ciable interval. The flask should be agitated throughout 
the titration. 

Since each cubic centimeter of the potassium perman- 
ganate solution is equal to 0.00375 gram of uric acid, the 
number of cubic centimeters of permanganate solution multi- 
plied by 0.00375, plus the correction of one milligram for 
each 15 c.c. of liquid present, w^ill give the amount of uric 
acid in the 100 c.c. of urine used. Fromi this the quantity 
of uric acid in the twenty-four-hour urine can be readily 
calculated, 

2. Acid Urines Containiitg Cystin. — The author recom- 
mends the addition of a small amount of ammonic hydrate ; 
heat and filter. The ammonium chloride may be added 
while the urine is still warm. 

J. Alkaline Ujdnes with an Abundant Deposit of Phos- 
phates. — Filter off the phosphates after complete precipita- 
tion by heat. The ammonium urate separates more rapidly 
in alkaline than in acid urine. The only objection to adding 
ammonic hydrate in all cases is its tendency to precipitate 
the phosphates. 

/J.. Albuminous Uri7ies. — Albumin does not interfere with 
the accurate determination of uric acid by this method, but 
requires a little longer digestion with an excess of hydro- 
chloric acid, in order to form the soluble acid-albumin. 



URIC ACID. 71 

5. Highly Pigmented Urine. — The pigment should be 
removed from the urate precipitate by treating thoroughly 
with alcohol, and after acidulation the filtrate is gradually 
heated to boiling and then digested for some time on a 
water-bath. The separated crystals are then thoroughly 
washed. 

In a urine containing bile the biliary pigment may come 
down in considerable quantity ; but despite this, the ultimate 
error is small. 

Folin's Method. ■'^ — This process depends upon the pre- 
cipitation of uric acid as ammonium urate, by means of 
ammonium sulphate, and is conducted as follows : 

Process. — To lOO c.c. of filtered urine add 10 grams of 
ammonium sulphate ; allow it to stand two hours, filter, 
and wash the urate precipitate with a ten per cent, solution 
of ammonium sulphate until it is free from chlorine. Dis- 
solve the entire urate precipitate in hot distilled water, add 
to this solution 15 c.c. of concentrated sulphuric acid, and 
then titrate, while hot, with a twentieth-normal solution of 
potassium permanganate, each cubic centimeter of which 
corresponds to 0.00375 gram of uric acid. Read off the 
number of cubic centimeters of permanganate solution 
used, multiply by 0.00375, and to the result add one milli- 
gram for correction. This equals the amount of uric acid 
in 100 c.c. of urine. From this calculate the quantity for 
twenty-four hours. 

According to Hofmeister,^ neither albumin nor globu- 
lin are precipitated by a ten per cent, solution of ammonium 
sulphate. 

Quantitative Estimation of Uric Acid by the Centri- 
fuge. — The following method, devised by Dr. R. Harvey 
Cook, ^ promises excellent results and has the advantages of 
being rapid and quite accurate. It is based, chemically, 
on the method of Haycraft, in that the uric acid is pre- 
cipitated as urate of silver. 

The following apparatus are necessary : a centrifuge, four 
graduated tubes of a capacity of 15 c.c. each, and a pipette 
holding one cubic centimeter. 

Process. — Place 10 c.c. of urine in the graduated tubes, 
add to this from 0.5 to i gram of crystals of sodium car- 

^ " Zeitschr. f. physiol. Chemie," Bd. xxiv, 3, S. 224. 

2 <' Archiv f. exp. Pathol, u. Pharm.." Bd. xxv, 247, 1888. 

3 '< Medical Record," March 12, 1898, p. 373. 



72 ORGANIC CONSTITUENTS OF NORMAL URINE. 

bonate, and i or 2 c.c. of ammonium hydrate. Shake 
until the sodium carbonate is dissolved ; this precipitates 
the earthy phosphates. Separate this precipitate in the 
centrifuge, and decant all of the supernatant clear urine 
into another graduated tube. To the clear urine, now 
free from phosphates, add 2 c.c. of ammonic hydrate and 
2 c.c. of an ammoniacal solution of silver nitrate made by 
dissolving 5 grams of silver nitrate in lOO c.c. of distilled 
water, and adding ammonic hydrate until the solution be- 
comes clear. 

The addition of the silver solution causes the uric acid to 
be precipitated as the urate of silver — a translucent, slimy 
substance. Separate this precipitate in the centrifuge, pour 
off the supernatant urine, and add to the precipitate an 
excess of ammonic hydrate — at least 5 c.c. — and mix thor- 
oughly. By this last step any of the chlorides that may 
have been precipitated are redissolved, leaving only pure 
urate of silver. Lastly, centrifugalize again until the silver 
urate precipitate has fallen as low as it will go. 

Each 3^ of a cubic centimeter as marked on the gradu- 
ated tube is equivalent to o.ooi 176 gram of uric acid in 10 
c.c. of urine. For example: if 0.5 be the lowest reading 
obtainable, then 5 X 0.001176 — 0.00588 gram of uric 
acid in 10 c.c. of urine. In order to obtain the per- 
centage, multiply this result by 10 ; if the twenty-four- 
hour quantity of urine be known, the total uric acid can be 
easily calculated. 

XANTHIN BASES* 

A number of xanthin bases have been found in urine : 
Xanthin, CgH^N^Og ; Heteroxanthin, CgHgN^Og ; Paraxan- 
thin, C^HgN^Og ; Guanin, CgH^NgO ; Hypoxanthin (sarkin), 
QH^Np ; Adenin, CH^N^ ; Episarkin, C^HgNgO ; Carnin, 
CyHgN^g ; Epiguanin, C^qHj3N902 ; and, finally, an un- 
known base discovered by Kriiger. 

The xanthin bases have also been called nuclein bases (Kos- 
sel) and alloxur bases (Kossel and Kriiger). The alloxur bases, 
together with uric acid, have been given the names alloxur 
bodies (Kossel and Kriiger) and purin bodies (E. Fischer). 

Kriiger and Salomon ^ have recently made an extensive study 
of the alloxur bases. From 10,000 liters of urine they obtained 

1 **Zeitschr. f. physiol. Chemie," Bd. xxvi, 1898, S. 350. 



XANTHIN BASES. 



73 



the following: Xanthin, lo.ii gm.; heteroxanthin, 22.345 
gm.; 1-methylxanthin, 31.285 gm.; paraxanthin, 15.31 gm.; 
hypoxanthin, 8.50 gm.; adenin, 3.54 gm.; and epiguanin, 
3.4 gm. The bases adenin, hypoxanthin, and xanthin, due 
to the breaking down of nuclein, occur in smaller quantities 
than the homologues of xanthin which are probably derived 
from the theobromin, caffein, and theophyllin introduced into 
the system by the use of tea and coffee, paraxanthin being 
obtained from caffein, heteroxanthin from theobromin, and 
1-methylxanthin from theophyllin. 

A brief consideration of the most important of the 
xanthin bases follows. ^ 

Xanthin (QH^N^OJ, — When pure xanthin is dissolved 
in a weak alkali with the aid of heat, strongly diluted 




Fig. 8. — Xanthin crystals (after the drawings of Horbaczewski, as represented in 
Neubauer and Vogel). 



(i : 2000), and then saturated with acetic acid, it crystallizes 
in macroscopic, colorless, glistening, rhombic plates, ar- 
ranged in groups. (Fig. 8.) Xanthin, which is separated 
from its concentrated aqueous solution by boiling, is amor- 
phous, but on standing soon collects in flakes, films, or crusts. 
Xanthin is soluble in 13,000 to 14,000 parts of cold 
water, and in 1300 to 1400 parts of hot water; it is diffi- 
cultly soluble in dilute alcohol and dilute acids, but much 
more soluble in ammonic hydrate than in water. On 
cooling, xanthin separates from its warm saturated solution 

1 For details see Neubauer and Vogel, Bd. i, 1898, S. 331. 



74 ORGANIC CONSTITUENTS OF NORMAL URINE. 

in ten per cent, ammonia in the form of fine needles of 
xanthin-ammonium. If xanthin be dissolved in very weak 
sodic hydrate, on standing small crystals of xanthin-sodium, 
CHgNaN^Og . H2O, separate. A solution of xanthin 
in ammonia gives, with an ammoniacal solution of zinc 
chloride, a white precipitate which is soluble in an excess 
of ammonia. Xanthin in crystalline form contains one 
molecule of water of crystalHzation ; when amorphous, it is 
water-free. If xanthin is heated in a closed tube, it sub- 
limes without melting, and results in a decomposition with 
the evolution of hydrocyanic acid. 

Xanthin is a constituent of normal urine, but is present 
only in traces. Kriiger and Salomon ^ found a maximum 
of only 13 grams in 10,000 liters of normal human urine. 
Stadthagen was able to isolate from the twenty-four-hour 
quantity of urine of a healthy individual on a mixed diet 
0.032 and 0.025 gram. 

Xanthin contains one atom less of oxygen than uric acid, 
to which it is closely allied. It has rarely been encountered 
as a constituent of the urinary sediment. It has been found 
as a constituent of a very rare form of calculus, and in those 
cases reported, was always observed in children. 

Xanthin is increased in leukemia (as high as 0.028 gram 
in 100 c.c.) ; Stadthagen found 0.07 gram in the twenty-four- 
hour urine as an average of seven determinations. Pouchet^ 
found it in unusual quantities in fever, and particularly in 
affections of the nervous system — pachymeningitis cervicalis 
hypertrophica and tabes dorsalis. 

Detection. — (i) When a solution of xanthin in a fixed 
alkali is added to sodium or calcium hypochlorite, nitrogen 
gas is evolved and the solution becomes green, changing to 
a brown and finally to a yellow. (2) When xanthin is 
heated to 200° C. with fuming hydrochloric acid, it is de- 
composed into glycocoll, ammonia, carbonic acid, and formic 
acid. (3) When evaporated to dryness with nitric acid, a 
yellow residue remains, which becomes violet on the addi- 
tion of potassium hydrate, the violet color increasing upon 
the application of heat. (See Murexide Test for Uric Acid.) 

Heteroxanthin (C5H3NP2 . CH3). — Heteroxanthin, 
when pure, crystalhzes from its hot aqueous solution in 

i^Zeitschr. f. physiol. Chemie," Bd. XXI, 169, 1895. 
2 ''Thesis," Paris, 1880. 



HVPOXANTHIN. 75 

glossy needles about a half centimeter in length, also in 
thorn-like spheres, and in thick columns which have a fan- 
like arrangement. It is soluble in 1 592 parts of water at 
18° C, in 109 parts of boiling water, and is sparingly 
soluble in absolute alcohol. When pure, it is insoluble in 
ether and chloroform ; but when impure, it is sparingly 
soluble in chloroform. It is readily soluble in ammonia and 
other alkalies. Heteroxanthin combines with sodium to 
form a double salt, prepared by the addition of sodic hydrate 
to its concentrated solution. 

Heteroxanthin is a constituent of normal urine, but is 
present only in minute quantities. Salomon found only i 
gram in 1000 liters ; Kriiger and Salomon isolated 7.5 
gram from 10,000 liters of normal human urine. 

Clinically, it is increased in leukemia, in phosphorus- 
poisoning, and following the ingestion of theobromin and 
caffein. 

Detection. — Heteroxanthin does not respond to the 
tests for xantbin. It gives an intense reaction with hydro- 
chloric acid and a trace of potassium chlorate ; the red 
residue changes to a violet on the addition of potassium 
hydrate (Weidel's test). 

Hypoxanthin (CH^Np). — Hypoxanthin, also termed 
sarkin, is present in normal urine, but only in minute quan- 
tities. Pure hypoxanthin does not crystallize in the form of 
needles, but always appears on the bottom and sides of the 
glass or on the surface of the fluid in the form of a film, as 
oval kernels with sharp angles. Like xanthin and hetero- 
xanthin, when heated in a closed tube it sublimes and 
evolves hydrocyanic acid. It is soluble in 300 parts of cold 
water and in 78 parts of hot water, also in 900 parts of hot 
alcohol. It is more readily soluble in ammonia than in 
water. It is not precipitated by saturating its solution with 
ammonium chloride. Hypoxanthin is precipitated from its 
solution in alkalies by carbonic acid. It combines with 
the salts of sodium, zinc, and calcium to form double 
salts. 

Hypoxanthin has been found in the normal urine of man 
by Salomon, Salkowski, and others. It is most abundant 
after a hearty meat diet (in dogs). It appears to be in 
larger quantities in the urine of leukemia than in that of 
health (Stadthagen isolated an average quantity of 0.009 
gram — as high as 0.027 gram — from leukemic urine), also 



76 ORGANIC CONSTITUENTS OF NORMAL URINE. 

in diseases of the liver and kidneys (Thudichum), and in 
fever and diseases of the central nervous system (Pouchet). 

Detection. — When hypoxanthin is treated with zinc 
and dilute hydrochloric acid, and then sodic hydrate is 
added, a red or reddish-brown color appears, the result of 
the absorption of oxygen from the air. Hypoxanthin does 
not give a green color with sodic hydrate and calcium 
hypochlorite as does xanthin. 

Paraxanthin (C5H2NP2(CH3)2). — Paraxanthin is iso- 
meric with theobromin and theophyllin. It crystallizes 
in colorless, glossy, six-sided plates. It is difficultly solu- 
ble in cold water, but dissolves much more readily in hot 
water, its solutions having a neutral reaction. It is insolu- 
ble in alcohol and ether. It combines with sodium to form 
a double salt, which has much the same general properties 
as the compound of sodium with heteroxanthin. 

Paraxanthin has been detected in the urine of man by 
Thudichum and Salomon. Like the other bases of this 
group, it was found in unusual quantities in leukemic urines. 
Comparatively little is known of the clinical significance 
of this substance. 

Detection. — Paraxanthin gives Weidel's test, but does 
not respond to the tests for xanthin. 

The isolation of the xanthin bases ^ is accomplished in four 
ways: (i) Precipitation with ammoniacal solution of silver 
nitrate ; (2) with copper suboxide ; (3) with phosphotungstic 
acid ; (4) with cupric acetate. 



NUCLEIC AQD. 

This acid has been found by Morner in very small 
quantities in the urine. It appears, however, in large 
amounts in combination with albumin as nucleo-albumin. 
(See p. 142.) The nucleic acids are compounds of phos- 
phoric acid, xanthin bases, and a nitrogen-free substance. 
Some of these compounds have been recognized as pentose 
and hexose. The amount of phosphorus in the nucleic 
acids varies, but may reach as high as 9 or 10 per cent. 
They are amorphous, have an acid reaction, are soluble in 
ammonia, in alkaline hydrates, or in distilled water holding 
a small amount of alkali, and are precipitated from their 

1 See Neubauer and Vogel, "Analyse des Hams," Bd. I, 1898, S. 362. 



ALLANTOIN. 77 

solutions by a small amount of hydrochloric acid, but 
not by acetic acid. They are, however, precipitated by an 
excess of glacial acetic acid. They are completely precipi- 
tated by alcohol in the presence of hydrochloric acid. Ac- 
cording to Kutscher, nuclein is precipitated from a neutral 
solution of the salts of nucleic acid by an aqueous solution 
of albumose. Noll ^ has recently succeeded in forming 
levulinic acid from nucleic acid by heating with thirty per 
cent, sulphuric acid for two hours. 

Nucleic acid is not precipitated by the reagents used for 
the precipitation of proteids, and does not give the color 
reactions of proteids. When some of the nucleic acids are 
boiled with dilute mineral acids, a substance (carbohydrate) 
is produced which reduces alkaline solutions of cupric 
oxide. 

The detection of the nucleic acids depends upon the iso- 
lation of their chief constituents — phosphoric acid and xan- 
thin bases. 

ALLANTOIN. 

C4H6N4O3. 

This substance has been found in the urine of infants 
within the first eight days after birth, in new-born calves 
(Wohler), and in the urine of man (Ziegler and Hermann). 

AUantoin, when pure, crystallizes in large monoclinic 
prisms with hexagonal bases, often arranged in star-like 
groups ; when impure, in warty and granular particles. It 
has a neutral reaction, is difficultly soluble in cold water 
(160 parts), more readily in hot water (30 parts), very sol- 
uble in alkaline hydrates, and, according to Salkowski, 
more readily soluble in a solution of piperazin than in 
water. It is insoluble in alcohol and ether. It combines 
with acids and bases to form salts. The compounds with 
silver oxide and mercuric oxide are particularly serviceable 
for the detection of allantoin. 

When a freshly prepared solution of allantoin in sodic or 
potassic hydrate is supersaturated with acetic acid, it is 
immediately precipitated. It then contains allantoic acid. 

Allantoin is obtainable from uric acid by oxidation with 
potassium permanganate : 

2C5H,N,03 + 2H2O -f O2 = 2C,H6N,03 -f- 2CO2. 
Uric acid. Allantoin. 

i'*Zeitschr. f. physiol. Chemie," Bd. xxv, S. 430. 



78 ORGANIC CONSTITUENTS OF NORMAL URINE. 

Allantoin is decomposed by heating with hydrochloric 
acid into allanturic acid and urea : 

QH^NPs + H^O = CaH.N.Og + CH,N,0. 
Allantoin. Allanturic acid. Urea. 

When allantoin is boiled with an alkali or baryta water, 
it furnishes first, as in the decomposition with acids, allan- 
turic acid and urea ; but the allanturic acid is further decom- 
posed into hydantoic and parabanic acids : 



2C3H,N,03 


=--C3HeNA4-C3H,NA. 


Allanturic 


Hydantoic Parabanic 


acid. 


acid. acid. 



and the parabanic acid is finally decomposed into oxalic 
acid and urea : 

C3H2N2O3 -f 2H2O = C.HsO, + CH^Np. 

Oxalic Urea, 

acid. 

Allantoin reduces Fehling's solution on boiling. It is 
not precipitated by lead acetate or phosphotungstic acid, 
and does not give the murexide reaction, 

Allantoin is present in normal urine in mere traces, ex- 
cept directly after birth. It has been found to be increased 
by a meat diet, and by the administration of tannic acid. 
Pouchet found allantoin considerably increased in the urine 
of a case of diabetes insipidus and in a case of hysteria 
with convulsions. 

Detection. — In order to detect allantoin, it must first 
be separated from the urine. The following method of G. 
Meissner ^ best serves this purpose : Precipitate the urine 
with baryta water, exactly neutralize the filtrate with sul- 
phuric acid, filter at once, and evaporate to beginning 
crystallization. The fluid, while still warm, is treated with 
sufficient alcohol to completely precipitate (this precipitate 
should be saved). The alcoholic solution is then decanted 
from the precipitate or filtered off, and completely precipi- 
tated with ether. Both precipitates, especially the one ob- 
tained with the ether, contain the allantoin together with 
other substances. The precipitates are then extracted with 
a little cold water or with hot alcohol, the allantoin remain- 
ing undissolved. Characteristic cr}^stals of allantoin are 
then obtained by recrystallizing the residue from hot water. 

I'^Zeitschr, f. rat. Med.," [3] Bd. xxiv, 104, u. Bd. xxxi, 297. 



KREATIN AND KREATININ. 



KREATIN AND KREATININ. 

e4H9N302— C4H7N3O. 



These two substances are constituents of normal urine. 
They differ chemically in that kreatinin contains one mole- 
cule less of H.,0 than kreatin, as seen by the foregoing 
formulae. Kreatin, which is constantly present in muscle 
tissue, is in all probability the antecedent of kreatinin, so 
that two sources of this substance must be recognized — i. e., 
the muscle tissue of the body and the muscle tissue taken 
as food. Kreatin is more abundant in alkaline urine than 
kreatinin, while in a strongly acid urine the reverse is the 
case. Since the urine is generally acid, kreatinin is the pre- 




Fig-. 9. — Crystals of kreatinin-zinc chloride (Salkowski). 



dominating constituent of normal urine, and will be further 
considered. 

Kreatinm crystallizes without water of crystallization in 
colorless, glistening prisms of the monoclinic system ; some- 
times these crystals, when found lying on their sides, appear 
in the form of whet-stones. Kreatinin is readily soluble in 
hot water and quite soluble in cold water ; it is very solu- 
ble in hot alcohol, but more difficultly so in cold alcohol 
and ether. It reduces alkaline solutions of copper (Feh- 
Hng's solution) upon boiling. It forms salts with the acids, 
and double salts with some of the salts of the heavy metals. 
Among these may be mentioned kreatinin chloride or 



80 ORGANIC CONSTITUENTS OF NORMAL URINE. 

hydrochlorate, which is easily soluble in water and crystal- 
lizes in the form of transparent prisms or rhombic plates. 
One of the most important of the double salts is the com- 
pound of kreatinin with zinc chloride (C4H^N30)2 . ZnCl2, 
produced by treating an aqueous or alcoholic solution of 
kreatinin with zinc chloride. If the kreatinin is pure, the com- 
pound crystallizes in the form of fine needles grouped together 
in rosettes or sheaves. (Fig. 9.) Kreatinin -zinc chloride 
is very slightly soluble in water and insoluble in alcohol. 

Kreatinin is a constituent of normal human urine. Ac- 
cording to the determinations of Neubauer, a healthy man 
on a well-mixed diet eliminates from 0.6 to 1.3 grams of 
kreatinin in twenty-four hours. As indicated, the quantity 
of kreatinin appears to vary according to the disintegration 
of muscle tissue in the body and the amount of meat 
ingested with the food. 

Clinically, it is excreted in increased quantity in acute dis- 
eases, such as typhoid fever, pneumonia, etc. It is diminished 
in hunger, in convalescence from acute diseases, in advanced 
degeneration of the kidneys, and in wasting diseases. 

Detection of Kreatinin. — i. Weyl's Test. — To a few 
cubic centimeters of the urine add a few drops of a very 
dilute solution of sodium nitroprusside, and render alkaline 
with sodic hydrate. If kreatinin be present, the mixture 
assumes a ruby-red color, which disappears in a few minutes 
and is replaced by an intense yellow color, w^hich, on 
warming with glacial acetic acid, gives rise to a green color. 
The presence of albumin and sugar does not interfere with 
the reaction. 

2. To a solution of kreatinin add a small quantity of an 
aqueous solution of picric acid, and then a few drops of 
dilute sodic or potassic hydrate. An intense red color ap- 
pears. This red color is apparent (only less intense) when 
kreatinin is present in the proportion of i : 5000 ( Jaffe). 

3. When a solution of kreatinin is acidulated with nitric 
acid and treated with phosphomolybdic acid, a yellow, 
crystalline precipitate is produced, which is soluble in hot 
nitric acid. 

4. The double compound of kreatinin and zinc chloride 
shows, microscopically, characteristic crystals. (Fig. 9.) 
This test is used for the quantitative estimation of kreatinin. ^ 

1 See Neubauer and Vogel, ''Analyse des Harns," Bd. i, 1898, S. 396. 



HIPPURIC ACID. 81 



THE AROMATIC SUBSTANCES IN URINE. 

The aromatic substances that occur in urine belong to 
four classes : 

1. Hippuric acid, and similar aromatic compounds of 
glycocoll. 

2. Combinations of glycuronic acid with aromatic sub- 
stances. (See p. 171.) 

3. Aromatic oxyacids. 

4. Ethereal sulphates. 

Hippuric Acid (CgHgNOg). — Hippuric acid is a constitu- 
ent of the urine of man in both health and disease. The 
twenty-four-hour quantity of urine contains between o.i 
and I gram It is very abundant in the urine of herbivora, 




Fig. 10.— Hippuric acid crystals. 

and in man the quantity varies largely according to the 
amount of vegetable food ingested. It is absent from the 
urine of carnivora. 

Hippuric acid crystallizes either in the form of fine 
needles or four-sided prisms and pillars, the ends of which 
terminate in two or four planes. (Fig. 10.) At times these 
resemble the crystals of ammonio-magnesium phosphate, 
with which they should not be confounded. Typically, the 
crystals of hippuric acid are in the form of vertical rhombic 
prisms. 

Hippuric acid is soluble in 600 parts of water at 0° C, 
and much more soluble in hot water and alcohol. Its solu- 
tions have a strongly acid reaction. It combines with bases 
to form salts. Its compounds with the alkalies and alkaline 
earths are soluble in water and alcohol, but the silver, cop- 
per, and lead salts are difficultly soluble in water. Strong 
acids precipitate the hippuric acid from its salts, and it 
6 



82 ORGANIC CONSTITUENTS OF NORMAL URINE. 

reappears in crystalline form. When hippuric acid is boiled 
with an alkaline hydrate or with mineral acids, it takes up 
a molecule of water and is decomposed into benzoic acid 
and glycocoll : 

CgHj . CO — HN . CH, . COOH -f Hp = 
Hippuric acid. 

CfiH^ . COOH + H^N . CH2 . COOH. 
Benzoic acid. Gh-cocoll. 

This same decomposition takes place during the alkaline 
fermentation of the urine, especially of urine containing 
albumin, the hippuric acid being acted upon by the micro- 
coccus ureae. No hippuric acid, therefore, is found in 
decomposing urine, benzoic acid taking its place. Hippuric 
acid reduces alkaline solutions of cupric oxide (Fehling's 
solution) on boiling. 

The experiments of Meissner and Shepard, and of 
Schmiedeberg and Bunge show that hippuric acid is prob- 
ably formed by the union of benzoic acid and glycocoll, 
and that this union takes place in the kidneys, as they 
failed to find that the synthesis occurred after the removal 
of the kidneys. 

As previously indicated, the amount of hippuric acid in 
the urine of man is dependent chiefly upon the character 
and quantity of food ingested, being increased by a vege- 
table diet, especially by certain fruits, as prunes, mulberries, 
cranberries, blueberries, or by any substance containing the 
benzoic acid radicle. It is increased by the administration 
of benzoic acid, cinnamic acid, oil of bitter almonds, salicylic 
acid, toluol, etc. ; also in acute febrile diseases, hepatic dis- 
eases, diabetes mellitus, and cholera. It is diminished by 
an exclusive meat diet, although generally it does not dis- 
appear entirely from the urine upon such a diet. It is an 
interesting fact that, in accordance with Bunge's experi- 
ments on dogs, the elimination of hippuric acid appears to 
be wholly suspended in cases of acute and chronic paren- 
chymatous nephritis, following the ingestion of benzoic acid, 
which reappears in the urine unchanged. 

Detection. — When urine containing hippuric acid or one 
of its salts is evaporated to dryness with concentrated nitric 
acid, and the residue is heated in a test-tube, the odor of 
bitter almonds is noticed, due to the formation of nitro- 
benzol (benzoic acid gives the same result). 



AROMATIC OXYACIDS. 83 

Hippuric acid may be separated from urine containing an 
excess of it by evaporating the urine to one-fourth of its 
volume and acidulating with hydrochloric acid. In a few 
hours characteristic crystals of hippuric acid will be found 
in the deposit, when examined microscopically. 

Quantitative Estimation. — MetJiod. — From 500 to 
1000 c.c. of fresh urine are evaporated to a syrupy con- 
sistence on a water-bath, care being taken to keep the urine 
neutral by the addition of sodium carbonate. The residue is 
extracted with cold alcohol (ninety to ninety-five per cent.), 
taking a quantity about half as great as that of urine em- 
ployed, and setting aside the mixture for twenty-four hours. 
The alcoholic filtrate, which contains the salts of hippuric 
acid, is then freed from alcohol by distillation. The remain- 
ing solution is strongly acidulated with acetic acid, in order 
to Hberate the lactic acid, and extracted with at least five 
times its own volume of alcoholic ether (one part of alcohol 
to nine parts of ether). From the combined extracts the 
ether is distilled off and the remaining solution evaporated 
on a water-bath. The resinous residue is boiled with 
water, set aside to cool, and filtered through a well-moist- 
ened filter. The hippuric acid, which is easily soluble in 
boiling water, is thus separated from constituents that are 
soluble in alcohol and ether. The filtrate is rendered alka- 
line with a little milk of lime, any excess of calcium hydrate 
being removed by passing carbon dioxide through the mix- 
ture. This mixture is then brought to the boiling-point and 
filtered. Any impurities present are removed by shaking 
with ether. The calcium salts remaining in solution are 
decomiposed by means of an acid, and the solution is again 
extracted with ether. The remaining solution is evaporated 
to a few cubic centimeters, when the hippuric acid will sepa- 
rate on standing. The crystals are dried on plates of plaster- 
of-Paris ; they are then shaken with benzol or petroleum 
ether to remove any benzoic acid, and finally weighed. 
These crystals may be shown to be hippuric acid by their 
microscopic appearance, their solubility in alcohol, and 
their behavior when evaporated with concentrated nitric 
acid, as previously indicated. 

Aromatic Oxyacids. — Two of these, hydroparacumaric 
acid and paraoxyphenyl-acetic acid, are found in the urine 
in small quantities in combination with potassium. They 
apparently are derived from the decomposition that takes 



84 ORGANIC CONSTITUENTS OF NORMAL URINE. 

place in proteids in the intestine ; tryosin is probably an 
intermediate product (Baumann) : 



Tyrosin. Hydropara- 

cumaric acid. 

C9HJ0O3 = CgH.oO + CO2. 

Hydropara- Paraethyl 

cumaric acid. phenol. 

CgH^oO + 03 = CgHgOg + H,0. 
Paraethyl Paraoxy- 

phenol. phenyl-acetic 

acid. 

Ethereal Sulphates. — A few of the products of decom- 
position are of especial interest because of their behavior 
within the body, and because after their absorption they 
appear in the urine in the form of ethereal or conjugate sul- 
phates of sodium and potassium. A few, such as the oxy- 
acids, pass unchanged into the urine ; others, such as 
phenols, are changed into ethereal sulphates by synthesis, 
and are eliminated by the urine. Still others, such as indol 
and skatol, are converted into ethereal sulphates only after 
oxidation. The quantities of these bodies in the urine vary 
largely with the extent of the putrefaction that is constantly 
taking place in the intestine. 

The earliest information bearing upon this subject was 
furnished in 185 1 by Stadeler, who found that on distilling 
the urine of oxen and of men with dilute sulphuric acid, he 
obtained in the distillate small amounts of phenol. It was 
not, however, until 1875 that Baumann discovered that 
phenol existed in an ethereal combination with sulphuric 
acid. He also determined the presence of other ethereal 
sulphates, all of which were found to be compounds of the 
radicle HSO3. 

The ethereal sulphates appear to have one or both of two 
origins: (i) From the aromatic substances in the food; 
hence their greater abundance in the urine of herbivora. 
(2) From the intestine as a result of putrefaction. They 
are absorbed from the intestine, pass into the blood, and 
are eliminated in the urine in combination with potassium 
and sodium as ethereal sulphates. 

A large number of determinations have been made rela- 
tive to the proportion of the ethereal sulphates to the 
ordinary (alkaline) sulphates in the urine of man, and the 
normal proportion may be stated as about i : 10. 



INDOXYL-POTASSIUM SULPHATE. 85 

In disease, whenever the putrefaction in the intestine or in 
other parts of the body is increased, the proportion of ether- 
eal sulphates rises. The investigations of G. Hoppe-Seyler 
are noteworthy, his results being summarized as follows : 

1. Deficient absorption of the normal products of digestion, 
such as occurs in peritonitis and tubercular disease of the intes- 
tine, leads to an increase of the ethereal sulphates in the urine, 
because the products of digestion undergo putrefactive changes, 
and the putrefactive products are absorbed. 

2. Diseases of the stomach, in which the food lies in the 
stomach a long time and undergoes fermentative changes, 
always lead to an increase of the ethereal sulphates in the urine. 

3. Simple constipation and typhoid fever do not produce this 
result. 

4. Putrefactive processes outside the alimentary canal, putrid 
cystitis, putrid abscesses, putrid peritonitis, etc., have the same 
result as putrefactive processes within the intestine. The amount 
of the ethereal sulphates is, moreover, in all cases proportional 
to the degree of the putrefaction, and is increased by the reten- 
tion and diminished by the discharge of putrid matter. 

It has been conclusively shown by these and other obser- 
vations that the best criterion of the occurrence and amount 
of putrefaction in the body is the relation of the ethereal 
sulphates to the total sulphates.^ 

Indoxyl-potassium Sulphate (CgHgNO . SO^ . OK), In- 
doxyl — Indican {?) — This substance is formed from indol, 
— CgH.N, — which is a product of the putrefaction of 
albuminous substances in the intestine. The indol is then 
absorbed from the intestine and enters the blood, where 
it becomes oxidized to indoxyl, — C^H^NO, — which imme- 
diately combines with potassium (and to a slight extent 
with sodium) sulphate to form indoxyl-potassium sulphate, 
in which form it is eliminated in the urine. 

By the oxidation of indoxyl-potassium sulphate indigo- 
blue is formed : 

2C8HgNKS04 + 02 = 2C8H5NO + 2HK . so,. 

Indoxyl-potassium Indigo-blue. Potassium hy- 

sulphate. drate sulphate. 

Indigo-red, which has the same elementary composition 
as indigo-blue, is also one of the products of the oxidation 
of indoxyl sulphate. 

Indoxyl is a constituent of normal human urine, as a 

1 For quantitative determination of ethereal sulphates, see p. 1 15. 



86 ORGANIC CONSTITUENTS OF NORMAL URINE. 

result of the natural intestinal putrefaction. It is absent 
from the urine of the new-born. 

Under ordinary conditions indoxyl does not contribute to 
the color of freshly passed urine. It may, however, become 
partially oxidized in the body, especially in disease, or oxida- 
tion may take place outside of the body during the am- 
moniacal decomposition of the urine, when it probably 
furnishes some color to the urine. In rare instances the 
indoxyl sulphate is completely oxidized within the body, 
and a blue color is imparted to the urine, due to the deposit 
of indigo-blue. Furthermore, indigo calculi have been 
found in the urinary tract following the long-continued 
separation of indigo from the urine, but such instances are 
of very rare occurrence. 

The quantity of indoxyl separated from the urine as in- 
digo-blue has been found to be between 0.005 ^.nd 0.025 
gram in the twenty-four-hour secretion of a healthy indi- 
vidual on a mixed diet (Neubauerand Vogel). The largest 
quantities excreted in health are observed after a liberal in- 
gestion of a meat diet, particularly the so-called red meats, 
while the smallest quantities have been found during the 
ingestion of a milk diet. 

Clinical Significance. — The clinical importance of in- 
doxyl rests chiefly upon its increased elimination, its dimi- 
nution having little or no importance. Indoxyl is increased : 
(i) In all cases of increased intestinal putrefaction, espe- 
cially that taking place in the small intestine. Thus, in 
diarrhea it is increased, whereas in dysentery (disease of 
the large intestine) no such increase takes place. It is in- 
creased in typhoid fever and in cholera, also in some forms 
of Bright' s disease, notably chronic diffuse, chronic inter- 
stitial, and subacute glomerular nephritis. Simon has ob- 
served an increase in cases in which the gastric juices 
contained an abnormally small amount of free hydrochloric 
acid or in which it was absent entirely, notably carcinoma of 
the stomach, and he believes that it is possible to form a 
fairly accurate idea of the amount of free hydrochloric acid in 
the stomach by examining the urine for indoxyl. There are 
exceptions to this, however, to explain which he grants is im- 
possible at the present time. Indoxyl is also increased in 
acute, subacute, and chronic gastritis of whatever origin ; in 
acute peritonitis (marked increase), cancer of the mesentery, 
appendicitis, diseases of the liver and pancreas, especially 



INDOXYL-POTASSIUM SULPHATE. 87 

those accompanied by an acute peritonitis ; in Addison's 
disease, lead colic, and, in short, in any disease of the ab- 
dominal viscera accompanied by an increase in the intestinal 
putrefaction. It is also increased in acute diseases elsewhere 
in the body, as in pneumonia, pleurisy, meningitis, acute 
articular rheumatism, etc. 

(2) The indoxyl is increased by any condition that pre- 
vents the passage of fecal matter through the small intes- 
tine, as in intussusception, twists, new growths, and the like. 
In diseases of the large intestine an increase of indoxyl is 
never seen ; thus, the tests for indoxyl in the urine are of 
decided value in the differential diagnosis. In simple, un- 
complicated constipation the indoxyl is not increased. 

(3) i\n increase in the indoxyl is also seen when albu- 
minous putrefaction takes place in other parts of the body, 
as in cases of empyema, putrid bronchitis, gangrene of the 
lungs, advanced phthisis, etc. 

There can be no doubt of the clinical significance of the 
test for indoxyl in the urine, for points of decided importance, 
not only in diagnosis, but also in prognosis and treatment, 
can thus be gained. 

Detection. — (i) The following color reaction depends 
upon the decomposition and oxidation of the indoxyl-sul- 
phate of potassium by means of hydrochloric acid, the 
oxidation being accelerated by the use of nitric acid. The 
color that results usually consists of a mixture of indigo- 
blue and indigo-red (amethyst). 

Take 1 5 c.c. of strong hydrochloric acid (C. P.) in a wine- 
glass, add one or two drops of strong nitric acid (C. P.), 
stir, then add thirty drops of the urine to be tested, and 
stir immediately. An amethyst color soon makes its ap- 
pearance, reaching its greatest intensity in from five to 
twenty minutes. The amount of color obtained at the point 
of greatest intensity furnishes some data as to the amount 
of indoxyl present. If normal^ a distinct but not intense 
amethyst color appears ; if increased, the color is decided 
and often very deep ; and if diminished, there will be but 
very little color, and rarely an entire absence of color. 

The reaction can also be obtained by using hydrochloric 
acid alone, but has the disadvantage of requiring a longer 
time for the greatest color to appear. It is, therefore, ad- 
visable to add one or two drops of nitric acid in order to 
hasten oxidation, care being taken not to add more, or the 



88 ORGANIC CONSTITUENTS OF NORMAL URINE. 

oxidation will be so rapid that the amethyst color can not 
be seen, only a yellow color resulting.^ 

The thirty drops of urine added should always be uni- 
form in size, and such as are obtained when the urine is 
dropped from the lip of a urinometer-glass. (Fig. 2.) It 
is, therefore, advisable to have a pipette for the perform- 
ance of the test, made by dropping thirty drops of urine 
into a wune-glass, then drawing it up into the pipette, and 
indicating the level of the urine by means of a scratch on 
the glass. 

In urine containing potassium iodide the test for indoxyl 
can not be satisfactorily applied, particularly if hydrochloric 
acid containing free hydrochloric-acid gas be used, or if 
nitric acid be added to the hydrochloric acid. This is 
because of the oxidizing action of the iodine that is set 
free. Under such circumstances a yellow color imme- 
diately results ; in other words, the oxidation is so rapid 
that the amethyst color can not be seen. 

(2) Take about 10 c.c. of the urine in a test-tube, add an 
equal volume of hydrochloric acid and a few drops of a 
freshly prepared saturated solution of sodium hypochlorite, 
calcium hypochlorite, or common saltpeter, and then i or 2 
c.c. of chloroform. The mixture is thoroughly agitated and 
set aside. The indigo that has been set free is taken up 
by the chloroform, coloring this to a greater or less extent, 
the degree of increase as compared with the normal being 
determined by the intensity of color. 

Albumin does not interfere wdth these two tests. Bile 
pigment, which interferes with the reaction, may be removed 
by the addition of a solution of basic acetate of lead, care- 
fully avoiding an excess. Urines presenting a very dark 
color may be freed from the greater part of their coloring- 
matter in the same manner. If potassium iodide be present, 
the chloroform will be colored more or less of a carmine, 
owing to the liberation of free iodine. 

Skatoxyl-potassium Sulphate (C^HgNO . SO^K ).— 
This substance is formed from skatol, which, like indol, is a 
product of the putrefaction of proteids in the intestine. 
Some of it is absorbed by the blood, where it combines 
with potassium sulphate, in which form it is eliminated in 

^ If hydrochloric acid containing much free hydrochloric-acid gas be used 
for the test, nitric acid should not be added, since the oxidation is effected by 
the free gas present. 



PHENOL-POTASSIUM SULPHATE. 89 

the urine as a colorless compound, and when it is oxidized, 
it yields a red color. 

Skatoxyl-potassium sulphate is a constituent of normal 
urine, but is usually present in smaller quantities than the 
indoxyl sulphate. 

Clinically, this substance is of little interest except in 
connection with indoxyl, and since both the skatoxyl and 
indoxyl sulphates are, clinically, considered as one, it is not 
necessary here to enter into the consideration of its proper- 
ties or modes of detection further than to state that the 
indigo-red oxidation products obtained ' in the tests for 
indoxyl are probably partly due to the presence of skatoxyl- 
potassium sulphate. 

Phenol-potassium Sulphate {Cflfi SO3 . K).— Phenol, 
C^HgO, is one of the products of intestinal putrefaction. 
The production of phenol probably takes place lower down 
in the small intestine than indol, but higher up in the intes- 
tine than skatol. It is absorbed from the intestine, and, 
entering the blood, combines with potassium sulphate to 
form the ethereal or conjugate sulphate, phenol-potassium 
sulphate. According to Baumann, some of the sulphate 
comes from tyrosine, which passes through the stages of 
parakresol and paraoxybenzoic acid before conversion into 
the phenol salt. This substance is the form in which all 
of the phenol or carbolic acid of the body exists. It is a 
constituent of normal urine, and is present in amounts vary- 
ing between 0.017 and 0.5 gram — an average of about 0.03 
gram — for twenty-four hours. Phenol sulphuric acid is 
abundant in the urine of herbivora. 

A urine rich in indoxyl usually contains an excess of 
phenol, but one rich in phenol does not always contain an 
excess of indoxyl. In those cases in which an increased 
elimination of ethereal sulphates is due to albuminous putre- 
faction in other parts of the body than the intestine, as in 
empyema, pulmonary gangrene, putrid bronchitis, etc., an 
increased elimination of phenol alone may be noted, the 
amount of indoxyl being about normal. 

Clinical Significance. — The use internally or externally 
of large amounts of carbolic acid, lysol, salol, and other 
phenol compounds results in an increase in the amount of 
phenol sulphate and a corresponding diminution in the ordi- 
nary sulphates, the latter being taken up by the excess of 
phenol in the blood. Two substances, pyrocatechin and 



90 ORGANIC CONSTITUENTS OF NORMAL URINE. 

hydrochinon, are formed as a result of the splitting up of 
carbolic acid. Urines containing these substances, although 
usually normal in color when voided, become smoky, dark 
brown, or black on standing exposed to the air. This dark 
color is often more pronounced after alkaline decomposition 
begins, and is, in all probability, due to the oxidation pro- 
ducts of hydrochinon. 

The phenol sulphate is increased in those conditions that 
cause increased putrefaction in the lower part of the small 
intestine and upper portion of the large intestine. In other 
words, most of the conditions that cause an increase in 
the indoxyl sulphate also cause an increase in the phenol 
sulphate. Its increase is especially marked in peritonitis, 
pyemia, and in phosphorus-poisoning. 

Detection. — Distil the urine with sufficient sulphuric 
acid to make a five per cent, mixture, (i) To a portion of 
the distillate add bromine water, which gives a }'ellow pre- 
cipitate of tribromphenol. (2) To another portion add Mil- 
Ion's reagent, and heat. A beautiful red color results. 
(3) Saturate still another portion of the distillate with sodic 
carbonate in the cold, and shake with ether in order to 
remove salicylic acid and other substances that give a ferric 
chloride reaction. Evaporate the ether, and to an aqueous 
solution of the residue add ferric chloride, which gives a 
deep violet color. 

Determination. — The following procedure may be ap- 
plied for the determination of phenol in urine : Take 500 to 
1 000 c.c. of the urine, treat with sufficient sulphuric acid to 
represent five per cent, of the mixture, and distil as long as 
a specimen of the distillate is rendered cloudy by bromine 
water (i : 30), the specimens used for this purpose being 
carefully preserved. The total quantity of the filtered dis- 
tillate, together with the specimens that have been set 
aside, is now treated with bromine water, shaking the mix- 
ture after each addition of the reagent until a permanent 
yellow color results. After two or three days the precipi- 
tate of tribromphenol that forms is collected on a filter that 
has been previously dried and weighed, washed with water 
containing a trace of bromine, and then dried over sulphuric 
acid and weighed. One hundred parts of tribromphenol 
correspond to 28.4 parts of phenol. 

The urine contains small quantities of two other ethereal 
sulphates : i. e., kresol-potassium sulphate and katechol-potas- 



UROBILIN. 91 



si7iui sulphate. These have practically the same significance 
as those already considered, so that only mere mention here 
is necessary. For a detailed consideration of these sub- 
stances see Neubauer and Vogel, "Analyse des Harns," 
Bd. I, 1898, S. 156 and 158. 



URINARY COLORING-MATTERS. 

Urobilin (C32H^qN^O.). — Normal urobilin was first isolated 
fi-om the urine by Jaffe (1868). Although this substance 
has for a long time been considered the chief coloring- 
matter of the urine, it probably contributes very little to the 
color of the freshly passed urine of a healthy individual. 
Normal urobilin is present in the urine chiefly as a chro- 
mogen, — urobilinogen, — and it is not until this chromogen 
is decomposed that its color is set free. In many pathologic 
conditions, on the other hand, there appears to be a larger 
amount of free urobilin than normally, and to this MacMunn 
has given the name ''pathological urobilin." This can be 
artificially prepared from normal urobilin by the action of 
reducing agents. 

Normal urobilin is amorphous and not deUquescent. Its 
color varies according to the method of isolation : that pre- 
cipitated by means of ammonium sulphate is brown ; that 
precipitated upon the addition of an acid to its alkaline 
solution is red ; and that obtained by the evaporation of its 
alcoholic solution is reddish-brown. It is readily soluble in 
alcohol and chloroform, also in ether, acids, and ammonic 
hydrate. It is very sparingly soluble in water. Neutral 
salts increase its solubility in water, but by saturating its 
solution with some of these salts it is more or less com- 
pletely precipitated. It combines with alkalies to form 
salts, and is precipitated from solutions of these salts upon 
the addition of acids. 

When an acid solution of normal urobilin is examined 
with the spectroscope, it shows a broad absorption band to 
the right of E, the left border of which reaches nearly to 
b, while the right border incloses F. In alkaline solu- 
tion it shows a less broad absorption band between E and F^ 
inclosing b. (Fig. 1 1.) 

The origin of urobilin has been the subject of much dis- 
cussion. Two theories have been advanced: (i) That 
urobilin is formed from the bilirubin which enters the in- 



92 



ORGANIC CONSTITUENTS OF NORMAL URINE. 



testine with the bile, is there acted upon by the nascent 
hydrogen resulting from fermentation, a reduction product 
being formed which is absorbed and eliminated by the kid- 
neys ; (2) that urobilin is formed rather as the result of oxi- 
dation processes by means of the nascent oxygen in the 
intestine, or elsewhere in the body, than by a process of 
reduction. This theory- was originally advanced by ]\Iac- 
Munn, who based his view^ chiefly on the fact that by the 
action of hydrogen peroxide on acid hematin he was able 
to prepare an artificial product which showed the same 
spectroscopic appearances as normal urobilin. Hoppe- 
Seyler had previously prepared an artificial urobilin from 
hemoglobin, and also from hematin, by the action of tin 



m m 




Fig. II. — I, Acid urobilin; 2, alkaline urobilin (after Neubauer and Vogel). 



and hydrochloric acid. Whether stercobilin and urobilin 
are to be looked upon as products of reduction or oxidation 
must, therefore, still be regarded as unsettled. The most 
important point to notice, however, is that urobilin may 
originate either from bile pigment or from blood pigment. 
It has been conclusively proved that the bile pigment is 
formed from hemoglobin ; and that in nearly all diseases of 
the liver accompanied by jaundice, urobilin is largely in- 
creased in the urine. Furthermore, that those conditions 
which are attended with a destruction of the blood-corpus- 
cles are accompanied by an increased amount of urobihn in 
the urine. It is, therefore, safe to infer that the amount of 
urobilin in the urine is a measure of the destruction of the 
hemoglobin, or blood pigment. 



UROCHROME. 93 

The average quantity of urobilin in the twenty-four-hour 
urine, under normal conditions, is 123 milligrams ; in dis- 
ease the quantity may reach 800 milligrams. The excre- 
tion of urobilin is greater in the tropical than in the temper- 
ate climates (Lawson). 

Clinical Significance. — Urobilin is increased in acute 
infectious diseases, such as scarlet fever, pneumonia, erysip- 
elas, malaria, typhoid fever (moderately increased) ; also in 
acute sepsis, lymphangitis, acute articular rheumatism, appen- 
dicitis, atrophic cirrhosis and carcinoma of the liver, catarrhal 
icterus, lead coHc, and pernicious anemia. It is also in- 
creased in cases of poisoning by potassium chlorate, anti- 
pyrin, antifebrin, and pyridin. On the other hand, it is 
nearly absent from the urine in phosphorus-poisoning. 

Detection.! — Urobilin is best detected by means of the 
spectroscope: (i) Take from 10 to 20 c.c. of the urine, 
acidulate with a few drops of hydrochloric acid, and shake 
with from 6 to 10 c.c. of amyl alcohol. On spectroscopic 
examination the clear amyl-alcohol solution of urobilin 
show^s a characteristic absorption band of acid urobilin. 
(Fig. II.) (2) If to a small portion of this amyl-alcohol 
solution be added a few drops of a clear solution of i gram 
of zinc chloride in 100 c.c. of alcohol that has been ren- 
dered strongly alkaline with ammonia, a beautiful green 
fluorescence appears. This solution shows the spectrum of 
alkaline urobilin. (Fig. 1 1 .) 

For the isolation of urobilin the reader is referred to more 
extensive works on urinary analysis. 

Urochrome. — This substance is the chief coloring-matter 
of normal and pathologic urine, and imparts a yellow, orange, 
and even a brownish color to the urine. According to 
Garrod,^ a urate sediment always contains some urochrome, 

^ An old test, and one frequently applied for the detection and approximate 
estimation of urobilin, is the so-called urophaein test (^Heller') : Take about 
seven cubic centimeters of concentrated sulphuric acid in a wine-glass, and add 
twice the quantity of urine, which is poured into the acid from a height of 
about four inches. A garnet-red color appears which, if normal in amount, 
is so intense that only a little light can be seen through the mixture. If 
increased, the mixture is opaque, and if diminished, it is transparent. This 
test is most unsatisfactory, as normal coloring-matters other than urobilin are 
set free by the acid. This test is also modified by the presence of abnormal 
constituents, such as bile, sugar, etc. The test, therefore, is of very little, if 
of any, importance for the detection or approximate determination of urobilin 
in urine. 

2 "Journ. of Physiol.," xvii, 441, iSoS- 



94 ORGANIC CONSTITUENTS OF NORMAL URINE. 

either alone or with uroerythrin and other coloring-matters. 
The name iirochrome was first applied in 1 864 by Thudichum, 
^vho then considered it the chief coloring-matter of the 
urine. Urochrome is thought by some to consist of impure 
urobilin. It probably does contain some urobihn, but that 
it is an independent substance has been satisfactorily demon- 
strated by Thudichum, Garrod, and others. 

Urochrome contains nitrogen, but is free from iron. Its 
solutions have an amphoteric reaction. In a dry state it is 
amorphous, and has a brown color. It is odorless in the 
cold, but when heated over the water-bath it has a faint 
odor of urine. It is very readily soluble in water and alco- 
hol ; only sparingly soluble in acetic ether, amyl alcohol, 
and acetone; and is insoluble in ether, chloroform, and 
benzol. Its solution, on the addition of an acid, shows 
only a diffused absorption of the spectrum at the violet end. 
According to Thudichum, the acid alcoholic solution shows 
a faint, narrow absorption band between F and G, its left 
edge bordering on F. The neutral and alkaline solutions 
do not show absorption bands. It is precipitated by phos- 
photungstic and phosphomolybdic acids, acetate of lead, 
silver nitrate, mercuric acetate, and also by saturating its 
solution with ammonium sulphate. 

When uric acid is precipitated from a solution that has 
been treated with urochrome, the crystals are of a yellow or 
even brown color, and of the whetstone shape, the same as 
when they crj^stallize from the urine spontaneously. When 
uric acid is precipitated b\^ an acid from a solution con- 
taining urochrome, the cr\^stals are colored brown, the same 
as when they are precipitated from the urine by an acid. 

Detection. — Urochrome is recognized by the fact that it 
is precipitated from its solutions by ammonium sulphate, 
and that when it is decomposed by acids, it furnishes a 
brown or black substance. It is also distinguished by its 
color and spectrum. 

Urochrome is isolated, according to Garrod, by saturating 
the urine with am^monium sulphate, and extracting the pre- 
cipitate with absolute alcohol. According to Thudichum, 
it is best isolated by first precipitating the urine with a mix- 
ture of barium hydrate and acetate, and then treating the 
filtrate with lead acetate and ammonia. ^ 

1 See Neubauer and Vogel, " Analyse des Harns," Bd. I, 1 898, S. 508. 



UROERYTHRIN. 



95 



Uroerythrin. — This substance is a constituent of normal 
urine, and is usually present only in small quantities. It 
has been termed rosacic acid by Prout, and purpiirm by 
Golding Bird. 

Uroerythrin is free from iron, and when isolated, is amor- 
phous and of a brick-red color. It is soluble in amyl alco- 
hol, slightly soluble in acetic ether and absolute alcohol, 
and very difficultly soluble in water. Its solution in alco- 
hol soon decomposes. It is also decomposed by both oxi- 
dizing and reducing agents. Uroerythrin does not occur 
in the urine as a chromogen. When a urine is saturated 
with ammonium sulphate or chloride, uroerythrin is pre- 
cipitated with the ammonium urate. Its solutions are not 
fluorescent. It is extracted from a reddish urate sediment 
by boiling alcohol. 

Uroerythrin in dilute solutions shows two ill-defined ab- 



c J) 




a \ \ /3 

Fig. 12.— Spectrum of uroerythrin (after Neubauer and Vogel). 



sorption bands, one with its left border midway between D 
and E, its right border inclosing E {D 70 E — E 13 i^), and 
the other band with its left border to the right of b, and its 
right border inclosing F {E 44 F — F 9 G). (Fig. 12.) 
The right band is somewhat darker than the left, the light 
space between the two being rather ill defined. 

Uroerythrin, for the most part, exists in the urine in 
chemic combination with uric acid. It not only gives a 
yellow, or yellowish-red, color to uric acid crystals, but 
also colors a urate sediment pink or brick-red. 

Clinically, uroerythrin is increased in acute febrile dis- 
eases, such as pneumonia, influenza, typhoid fever, malaria, 
acute articular rheumatism, etc. ; in diseases of the liver, 
especially those in which there is a disturbance in the circu- 
lation ; in cirrhosis of the liver following the excessive use 



96 ORGANIC CONSTITUENTS OF NORMAL URINE. 

of alcohol ; and in chronic diseases of the heart and lungs. 
An increase of uroerythrin is usually accompanied by an 
increase of urobilin. 

Detection. — A deposit of amorphous urates having a 
pink or reddish color shows the presence of uroerythrin. 
On the addition of an alkaline hydrate its solution is imme- 
diately colored dark green. An amyl-alcohol solution of 
uroerythrin, obtained by shaking the urine with amyl alco- 
hol, shows the characteristic absorption bands. It is iso- 
lated by saturating the urine with ammonium chloride. 

Urorosein. — Urorosein does not occur in the urine as 
such, but as a chromogen, which, upon the addition of 
mineral acids, is gradually broken up, a rose-red color re- 
sulting. According to Robin, this substance is present in 
very small amounts in every normal urine, and in much 
larger quantities in certain diseased conditions. 

Urorosein dissolves in water with a resulting red color ; 
also in dilute mineral and many of the organic acids ; in 
alcohol and amyl alcohol. It is extracted from its aqueous 
solution by amyl alcohol, but not by ether, chloroform, 
benzol, or carbon disulphide. Its alcoholic solution shows 
a sharp and narrow absorption band between D and E {D 
48 E). Ammonia, hydrates of the fixed alkaHes, and alka- 
line carbonates immediately decolorize the red solution. 

The chromogen, according to Robin, crystallizes in color- 
less transparent needles when its concentrated alcohoHc 
solution is precipitated with ether. These crystals are 
readily soluble in alcohol and water, but not in ether or 
chloroform. It is incompletely precipitated by lead acetate. 

Clinically, urorosein is increased in the urine in diseases 
of the lungs (tuberculosis), pernicious anemia, and in cases 
of marked chlorosis. It is also increased in diabetes mel- 
litus, osteomalacia, typhoid fever, carcinoma of any of the 
abdominal viscera, appendicitis, nephritis, and especially 
in diseases of the stomach. It is increased by vegetable 
food. 

Detection. — (i) To 10 c.c. of the urine add 15 drops 
of concentrated hydrochloric acid, and if the urine be rich 
in urorosein, a rose-red color appears in the cold in about 
ten minutes ; the color appears more quickly when the 
mixture is heated to 70° C. (Robin). (2) Take from 50 to 
100 c.c. of the urine and add from 5 to 10 c.c. of 25 per 
cent, sulphuric acid. A reddish or rose-red color appears 



OXALIC ACID. 97 

in a few minutes. If this colored mixture is then shaken 
with amyl alcohol, the coloring-matter is removed (Nencki 
and Sieber). 

The spectroscopic examination of the amyl-alcohol ex- 
tract is indispensable for the certain detection of urorosein. 



OTHER ORGANIC CONSTITUENTS OF THE URINE, 

A number of organic constituents, in addition to those 
already described, may occur in small quantities in the urine. 
We may divide these into the following groups : 

1. Nonnitrogenous acids : oxalic, lactic, and succinic 
acids. 

2. Fatty acids. 

3. Glycerophosphoric acid (?). 

4. Carbohydrates : dextrose (see p. 147) and animal gum. 

5. Ferments : pepsin, trypsin. 

6. Mucin. 

Oxalic Acid (CgH^OJ. — Oxalic acid is usually, and per- 
haps always, a constituent of the urine in health, but is 
present in very small amounts (as high as 0.02 gram in 
twenty-four hours). Under pathologic conditions it appears 
in increased quantities in diabetes mellitus, organic diseases 
of the liver, and, indeed, in all conditions in which the oxi- 
dizing power of the system is decidedly interfered with, as 
in various diseases of the heart and lungs. 

Oxalic acid crystallizes with two molecules of H2O in 
colorless, rhombic prisms, which are readily soluble in water 
and alcohol. 

The greater part of the oxalic acid taken into or formed 
in the body exists in the form of a salt of calcium — calcium 
oxalate. 

Calcium Oxalate. — This salt crystallizes in two different 
forms according to the number of molecules of water it 
contains — i. e., crystals belonging to the monocHnic system 
— CgCaO^, H2O (small plates) — and those belonging to the 
tetragonal system — C2Ca04,3H20 (octahedra, etc.). The 
monoclinic crystals are seen when the salt rapidly separates 
from a concentrated solution ; the amorphous precipitate of 
calcium oxalate apparently has the same chemic composi- 
tion. The tetragonal crystals are seen when the salt slowly 
separates from dilute acid solutions. 

For a further consideration of this subject see page 219 
7 



98 ORGANIC CONSTITUENTS OF NORMAL URINE. 

Lactic Acid (CgHgOg) is not a constituent of normal urine. 
Liebig was unable to detect the slightest trace of it in 41, 42, 
and 56 liters of healthy urine. It does not appear in the urine 
after the administration of sodium lactate (Nencki and Sieber). 
It has been found in the urine in combination with bases in cases 
of acute yellow atrophy and marked cirrhosis of the liver, trichi- 
nosis, phosphorus-poisoning, and after severe muscular exertion. 
According to Colasanti and Moscatelli, it occurs in the urine as 
sarcolactic acid. 

Sarcolactic acid consists of a colorless, odorless, syrupy fluid, 
soluble in water, alcohol, and ether ; it is nonvolatile. The free 
acid rotates the plane of polarized light slightly toward the right, 
while solutions of its salts rotate the plane slightly toward the 
left (Wislicenus). Lactic acid is monobasic; it combines with 
bases to form salts, of which zinc lactate is the most important. 
Nearly all of its salts are soluble. 

For the detection of lactic acid see Neubauer and Vogel, 
''Analyse des Harns," Bd. i, 1898, S. 183. 

Succinic Acid (C^HgOJ has been occasionally found in the 
urine. Under ordinary conditions it probably exists in the 
urine chiefly in combination with sodium — sodium succinate. 
Succinic acid has been found in the urine especially after the 
ingestion of asparagus and asparagin. Baumann failed to find 
it after the ingestion of sodium succinate. 

Fatty Acids. — These consist of acetic, butyric, formic, and 
propionic acids. They are apparently free in the urine, and 
present only in mere traces (0.008 gram per diem). They can 
be increased to 0.9-1.5 gram by treating the urine with oxidiz- 
ing agents (v. Jaksch^). The amount of fatty acids also 
increases during the period of the ammoniacal fermentation 
(Salkowski 2). In certain febrile conditions they are increased 
to 0.6 gram, and in certain liver diseases may go as high as one 
gram per diem. This condition is called lipaciduria by v. Jaksch. 

Ferments. — Pepsin. — Several observers (Briicke, Sahli, 
Leo, and others) have found pepsin in the urine. The fol- 
lowing is an abstract of Leo's ^ work on the subject : 
'' Small pieces of fibrin soaked in the urine absorb the pep- 
sin, and on removing them to o. i per cent, hydrochloric 
acid, they are rapidly digested. Control experiments with 
fibrin not previously soaked in urine gave negative results. 
The morning urine was found to be richest in pepsin." 

Neumeister and Stadelmann have both shown that the 
ferment in the urine is true pepsin. 

1 "Zeitschr. f. physiol. Chem.," x, 536. 2 Jbid., xni, 264. 

3 "Pfluger's Archiv," xxxvn, 223, and xxxix, 246. 



FERMENTS. 99 

Trypsin. — This ferment is probably absent from normal urine, 
although Sahli claims to have found it. 

Mucm. — Much discussion has arisen as to whether the sub- 
stance that is nearly always present in very minute quantities in 
the urine is mucin or really nucleo-albumin. It is considered 
by some observers to be the chief constituent of the mucus de- 
rived from the muciparous glands of the urinary tract below the 
kidneys. Further, that it occurs in normal urine as a viscid, 
slimy substance, which is precipitated by the vegetable acids, 
especially acetic acid ; also by alcohol ; that it is free from 
phosphorus, and, when boiled with dilute acids, yields a sub- 
stance that reduces alkaline solutions. More recent observers 
consider it to be nucleo-albumin, and at the present time this 
theory is most tenable. (Seep. 142. ) The question, however, 
is unsettled, and needs further investigation. 



ofC. 



CHAPTER III. 

INORGANIC CONSTITUENTS OF NORMAL 
URINK 

The principal inorganic constituents of the urine are the 
chlorides, phosphates, and sulphates, which are in combina- 
tion Avith sodium, potassium, ammonium, calcium, and mag- 
nesium ; also traces of carbonates of the alkalies. There 
are also traces of iron, fluorine, and silicic acid, as well as 
free gases, including carbonic acid, nitrogen, and oxygen. 

The combined quantities of these various substances 
amount to between nine and twent\'-five grams in twenty- 
four hours. 

CHLORIDES. 

Chlorine exists in the urine chiefly as sodium chloride, 
although small amounts are in combination with potassium 
and ammonium. The chlorides, next to urea, constitute 
the chief solid constituent of the urine. They are derived 
from the food, — that is, the sodium chloride ingested Avith 
the food, — and under normal conditions practically all of 
this salt ingested is eliminated in the urine in an equivalent 
amount. 

The quantit}- of sodium chloride in the twenty-four-hour 
urine is normally between lo and 20 grams, and, calculated 
as chlorine, amounts to between 8 and 1 2 grams. A person 
ingesting food unusually rich in sodium chloride may elimi- 
nate more than 20 grams (XaCl), and the quantity may 
even reach 40 or 50 grams in the twent}'-four hours. On 
the other hand, if the amount of nourishment is diminished, 
a decrease in the elimination of the chlorides is observed. 
If this is carried to the point of star\'ation, the chlorides 
almost entirely disappear from the urine, the traces remain- 
ing being derived from the tissues and fluids of the body. 
The latter retain tenaciously a certain amount of sodium 

100 



CHLORIDES. 101 



chloride, and if, following a period of starvation, food con- 
taining sodium chloride is again taken, not all appears in 
the urine, but a portion is retained in the body until the 
original equilibrium is restored. A similar retention may 
be observed for a few days following the ingestion of large 
quantities of water, which, under ordinary conditions, causes 
an increased elimination of chlorides. 

An increased quantity of chlorine is due to an abundance 
of NaCl in the food, and is of no clinical importance. In 
diabetes insipidus, however, the increase of chlorine, which 
may reach thirty grams or more, is obtained at the expense 
of the body-fluids, and is, therefore, associated with marked 
emaciation. A dimimttion in the quantity of chlorine is in 
many instances of the greatest clinical importance. Such a 
diminution is often the result of disease, and not dependent 
entirely on a diminished quantity of salt ingested, although 
a low diet, naturally, has some effect on the quantity of 
chlorine eliminated. 

Clinical Significance. — The chlorides are diminished in 
the acute stage of all acute diseases, and especially those 
associated with a serous exudation or transudation (dropsy), 
vomiting, or diarrhea. One of the most important examples 
of this is pneumonia, in the acute stage of which, on 
account of the serous exudation, the chlorine is very low or 
may even be entirely absent from the urine. As soon as 
convalescence commences and the serous exudation begins 
to be absorbed, the chlorine reappears or gradually increases 
until it may, in a few days, exceed the normal temporarily. 
The test for chlorides is, therefore, of definite clinical value 
in determining the progress of the pneumonic process. The 
quantity of chlorine in the urine is very important in the 
differential diagnosis between acute meningitis and typhoid 
fever, the former being attended with a serous exudation, 
and hence a marked diminution in the chlorides, while in 
the latter they are only moderately diminished. The chlorine 
is markedly diminished or absent in cholera, pyemia, and 
puerperal fever, and also much diminished in acute articular 
rheumatism. 

In the convalescent stage of most acute diseases the 
chlorine gradually rises to normal, but is dependent chiefly 
on the appetite. 

The chlorides are diminished in all chronic diseases, more 
particularly in those attended with dropsy, when the}^ may 



102 INORGANIC CONSTITUENTS OF NORMAL URINE. 

be absent from the urine. In the chronic diseases without 
exudation or transudation the diminution in the amount of 
chlorine is in proportion to the amount of sodium chloride 
taken with the food — in other words, the quantity of 
chlorine may be looked upon as a measure of the appe- 
tite. If at any time during the course of a chronic disease 
accompanied by dropsy the fluid be absorbed, the quantity 
of chlorine in the urine slowly rises to near the normal, but 
only rarely does it exceed the normal, since the absorption 
of the serous fluid is usually very gradual. 

Detection. — The following test, which depends upon the 
precipitation of the chlorine by nitrate of silver, can be 
readily applied for the detection and approximate estimation 
of chlorides in the urine : 

Take one-half of a wine-glass of urine, underlie with a 
third as much concentrated nitric acid in the same manner 
as in the nitric acid test for albumin. (See p. 124.) Then 
add one drop of a solution of silver nitrate, — one part of 
silver nitrate and eight parts of water, — and if chlorides be 
present, a precipitate of silver chloride is formed. If the 
relative proportion of chlorides is normal or increased, a 
solid compact ball of silver chloride is obtained, which falls 
to the surface of the nitric acid. If the relative proportion 
is diminished, however, instead of forming a solid ball the 
silver chloride precipitate spreads out or becomes diffused to 
a greater or less extent through the layer of urine. 

This same test can also be applied by adding to one-half 
of a wine-glass of urine one or two drops of concentrated 
nitric acid, stirring the mixture, and adding one drop of the 
solution of silver nitrate (prepared as directed). If the result- 
ing precipitate quickly falls to the bottom of the glass in a 
solid, flaky mass and does not tend to diffuse through the 
urine, the chlorides are normal or increased ; if diffused, 
they are diminished. 

If the urine contains more than a trace of albumin, it 
must be removed by heat before the test is applied, for the 
following reasons : (i) The precipitate or ball of silver 
chloride can not be distinctly seen because of the cloud of 
precipitated albumin ; (2) the silver and albumin combine to 
form the albuminate of silver, thus modifying the inferences 
to be deduced from the test. 

Quantitative Tests. — (a) Mohr's Method. — Precipita- 
tion by silver nitrate. 



CHLORIDES. 103 

The following solutions are necessary : 

1. Standard Silver Nitrate Solution: Dissolve 29.075 
grams of fused silver nitrate in distilled water, and make 
the whole quantity up to exactly one liter (lOOO c.c). One 
cubic centimeter of this solution is equivalent to 0.0 1 gram 
of sodium chloride, or 0.006065 gram of chlorine. 

2. A solution of neutral potassium chromate, made by dis- 
solving one part of the chlorine-free salt in five parts of water. 

Process. — Take 10 c.c. of urine ; dilute with 50 c.c. of 
distilled water; add to this 8 or 10 drops of potassium 
chromate solution. Drop into this mixture from a burette 
the standard nitrate of silver solution. The chlorine com- 
bines with the silver to form silver chloride — a white precip- 
itate. When all the chlorine is precipitated, silver chro- 
mate (red in color) forms, but not while any chloride 
remains in solution. The silver nitrate solution must, there- 
fore, be added until a pink tinge appears. Read off the 
quantity of standard solution of silver used, subtract i c. c. 
for correction (see below), and calculate therefrom the 
quantity of chlorine, or sodium chloride, in the 10 c.c. of 
urine tested. From this deduce the percentage, or the 
total number of grams in the twenty-four-hour urine. For 
example, suppose that, after deducting i c.c. for correction, 
exactly 10.5 c.c. of the standard silver nitrate solution 
were used. Since i c.c. of this solution is equivalent to 
0.006065 gram of chlorine, 10.5 X 0.006065 =0.0636825 
gram, or the amount of chlorine in the 10 c.c. of urine 
used. 

Precautions and Corrections. — If the urine contains al- 
bumin, it must be removed by means of heat and acetic 
acid. 

Alkaline urines should be rendered acid, preferably with 
acetic acid, previous to the titration. 

The phosphate of silver is not precipitated in this test, as 
the silver salts of hydrochloric, chromic, and phosphoric 
acids are precipitated in the following order : chloride, 
chromate, and, finally, the phosphate. 

A highly colored urine may give rise to difficulty in de- 
tecting the pink tinge of the chromate of silver. This is 
overcome by diluting the urine to a greater extent than in 
the directions given. It is not always necessary to dilute 
a pale-colored urine to the extent previously stated, the addi- 
tion of 20 to 30 c.c. of water often being sufficient. 



104 INORGANIC CONSTITUENTS OF NORMAL URINE. 

One cubic centimeter should always be subtracted from 
the total number of cubic centimeters of silver nitrate solu- 
tion used, as the urine contains small quantities of certain 
compounds more easily precipitable than the chromate of 
silver. To obviate this error, Sutton has advised the fol- 
lowing modification of Mohr' s test : Take lo ex. of urine 
in a thin porcelain dish, and add i gram of pure ammonium 
nitrate. The whole is then evaporated to dryness, and 
gently heated over a small flame to low redness until all 
vapors are dissipated and the residue becomes white. It is 
then dissolved in a small quantity of water, and the carbon- 
ates produced by combustion of the organic matter neutral- 
ized by dilute acetic acid. A few grains of pure carbonate 
of calcium are added to remove all free acid, and then one or 
two drops of a solution of potassium chromate. The mix- 
ture is then titrated with decinormal silver solution (16.966 
grams of silver nitrate to the liter) until the pink color 
appears. Since each cubic centimeter of the silver solution 
represents 0.005837 gram of sodium chloride, the quantity 
of sodium chloride, or chlorine, can be readily calculated. 

The results obtained by direct titration of the urine with 
a standard solution of silver nitrate can not be considered 
absolutely accurate, since uric acid, xanthin bases, sulpho- 
cyanides, sulphites, coloring-matters, etc., are precipitated 
with the silver chloride before the end-reaction appears. 
To obviate such errors, Neubauer and Salkowski have ad- 
vised the following process : 

Neubauer- Salkowski Method. — The necessary solu- 
tions are to be prepared according to the directions given 
under Mohr's method. 

Take 10 c.c. of urine in a small platinum or porcelain 
crucible ; add one gram of sodic carbonate that is free from 
chlorine, and i or 2 grams of chlorine-free potassium nitrate, 
and evaporate to dryness at 100° C. Heat over a free 
flame — at first gently, later strongly — until the molten mass 
is perfectly white. Dissolve the white residue in distilled 
water, and transfer the solution to a small flask. To this 
alkaline solution add dilute nitric acid, drop by drop, until 
faintly acid, and then neutralize again with chlorine-free 
sodic carbonate. Add a few drops of the solution of potas- 
sium chromate to the mixture, and allow the standard solu- 
tion of silver nitrate to flow from a burette into the mixture 
in the flask, until the first appearance of a permanent pink 



CHLORIDES. 105 

tinge (end-reaction). Read the number of cubic centimeters 
of standard solution of silver used, and calculate therefrom 
the quantity of chlorine or sodium chloride in the lo c.c. 
of urine tested. 

Volhard and Falck Method. — This method depends 
upon the action of soluble sulphocyanides with solutions of 
silver and ferric salts. Soluble sulphocyanides produce in 
silver solutions a white precipitate of sulphocyanide of silver, 
which is insoluble in dilute nitric acid. A like precipitate 
of sulphocyanide of silver with a solution of nitrate of silver 
is given by the blood-red solution of sulphocyanide of iron, 
and the color of the latter at last completely disappears. 
If, therefore, a solution of sulphocyanide of potassium be 
added to an acid solution of nitrate of silver to which a 
little ferric sulphate has been added, every drop of the 
sulphocyanide solution at first produces a blood-red cloud, 
which, however, quickly disappears on stirring, while the 
fluid becomes milk-white. It is not until all the silver is 
precipitated that the red color of the sulphocyanide of iron 
remains permanent and the end of the process is reached. 

The following solutions are necessary : 

1. Standard solution of silver nitrate, made according to 
directions given under Mohr's method. One cubic centi- 
meter is equivalent to 0.006065 gram (6.065 milligrams) 
of chlorine, or 0.0 10 gram (10 milligrams) of sodium 
chloride. 

2. Solution of Ferric Oxide. — A cold, saturated solution 
of crystallized ferric alum free from chlorine, or a solution 
of ferric sulphate that contains 50 grams of oxide of iron 
to the liter. 

J. Standard Solution of Potassium Sidphocyanide. — Since 
potassium sulphocyanide can not be accurately weighed, 
because of its hygroscopic property, it is necessary to stand- 
ardize by titrating with a standard solution of silver nitrate. 
Dissolve 10 grams of potassium sulphocyanide in a little 
less than a liter of distilled water, and place a portion of 
this in a burette. Take 10 c.c. of the standard silver solu- 
tion, place in a beaker, add 5 c.c. of the iron solution, and 
then pure nitric acid, drop by drop, until the mixture is 
colorless. Then allow the sulphocyanide solution to flow 
in from the burette until the fluid has a permanent red color, 
the first appearance of which indicates the end-reaction — 
that is, when all of the silver is precipitated as silver sulpho- 



106 INORGANIC CONSTITUENTS OF NORMAL URINE. 

cyanide, the next drop gives a permanent red color, due to 
the precipitation of the sulphocyanide of iron. If, for ex- 
ample, to lo c.c. of the silver solution 9.6 c.c. of the potas- 
sium sulphocyanide solution have been used before the red 
color is permanent, 960 c.c. are measured off, and diluted 
with 40 c.c. of distilled water to make a liter. Titrate once 
more, in order to be sure that the strength of the two solu- 
tions — standard silver and potassium sulphocyanide solu- 
tions — is equivalent. 

Process. — Take 10 c.c. of urine, add i or 2 grams of 
potassium nitrate free from chlorine, and evaporate to dry- 
ness on a water-bath. The residue is then heated over a 
free flame — at first gently, afterward strongly — until the 
carbon is completely oxidized and the residue is a white 
mass. Since the nitrous acid formed in this process pre- 
vents the end-reaction, the fused mass is dissolved in water, 
acidulated with nitric acid, and then the chlorine precipi- 
tated with an excess of the standard solution of silver. 
After this mixture has been warmed on a water-bath for a 
time to remove completely the nitrous acid, it is allowed to 
cool. Then 5 c.c. of the iron solution are added ; and, 
finally, the potassium sulphocyanide solution, until the ex- 
cess of the silver added is precipitated, which is known by 
the permanent red color of the mixture. The difference be- 
tween the number of cubic centimeters of the silver and 
sulphocyanide solutions corresponds to the chlorine con- 
tained in the urine. If, for instance, at first 15 c.c. of the 
silver solution were added to 10 c.c. of urine, and 5 c.c. of 
the sulphocyanide solution were required to titrate back the 
excess, the amount of chlorine in the urine would corre- 
spond to 15 — 5 = 10 c.c. of the silver solution. 

(b) Purdy's Method, by the Electric Centrifuge. — 
The percentage tubes of the Purdy electric centrifuge are 
filled to the lo-c.c. mark with the urine to be tested; 
fifteen (15) drops of nitric acid are added to prevent precipi- 
tation of the phosphates (if the specific gravity be very high, 
20 to 30 drops should be added), and then the tubes are 
filled to the 15-c.c. mark with a strong solution of nitrate 
of silver (i : 8). The tubes are next closed, and inverted 
several times, until the urine and the reagents are thoroughly 
mingled. The tubes are then placed in the centrifuge, and 
revolved at the rate of 1000 revolutions a minute for 
three successive periods of five minutes each, when the 



PHOSPHATES. 107 

quantity in bulk percentage may be read off from the grad- 
uated scale on the sides of the tubes. Purdy has found 
that the bulk percentage of chlorides in normal urine thus 
obtained ranges from lo to 12 per cent. 

By a comparison of the bulk percentages of chlorides 
with the volumetric determinations of the same the author 
has been able to obtain, from a large number of observa- 
tions, a standard of percentage by zveigJit. He has found 
that each ^ of a c.c. of precipitate, calculated as chlorine, 
is equivalent to 0.123 per cent, by weight. 



PHOSPHATES. 

Phosphoric acid in the urine occurs in the form of two 
classes of phosphates : 

1. Earthy Phosphates : phosphates of calcium and mag- 
nesium, the former being the more abundant. 

2. AlkaHne Phosphates : phosphates of sodium and po- 
tassium, the former being the more abundant. 

The earthy phosphates, which consist of the phos- 
phates of the alkaline earths, — calcium and magnesium, 
— are insoluble in water, but soluble in acids. In an acid 
urine they are in the form of acid phosphates, which are 
in solution. Occasionally, a crystalline deposit of acid 
calcium phosphate (see p. 218) having the composition 
CaHPO^ + 2H2O (Hassal, Stein) separates from a faintly 
acid urine. 

In an alkaline urine the acid phosphates of magnesium 
and calcium are converted to normal phosphates, and are 
precipitated as a heavy, whitish sediment, frequently termed 
amorphous phosphates. A similar phosphatic precipitate is 
often obtained when a faintly acid, neutral, or alkaline urine 
is heated, owing to the conversion of the acid phosphate to 
normal phosphate, which is precipitated, and the superphos- 
phate, which remains in solution : 

4CaHP0^ = CaH^2P0^ + Q2.^2Y0^. 

This phenomenon is a frequent source of error in testing 
for albumin in urine by heat. If, upon heating, such a pre- 
cipitate appears, it may be readily distinguished from the 
precipitate of albumin by the addition of a few drops of 
acetic acid, which quickly dissolves the earthy phosphates. 
When a urine becomes aninioniacal, the phosphate of mag- 



108 INORGANIC CONSTITUENTS OF NORMAL URINE. 

nesium combines chemically with ammonia to form the 
mnrnonio-inagnesiimi phospJiate , or '* triple phosphate," which 
is in crystalline form. (See p. 217.) 

The alkaline phosphates consist chiefly of the phos- 
phates of sodium and potassium, which, unlike the earthy 
phosphates, are soluble in water and alkalies. The sodium 
salt — monosodic acid phosphate (the disodic acid phosphate 
is also sometimes present) — is much more abundant than 
the potassium salt, and, as previously stated, it is to this com- 
pound that the acidity of the urine is chiefly due. The 
alkaline phosphates form the chief bulk of the phosphates 
of the urine, being in excess of those combined with the 
alkaline earths, the proportion being between i ^ and 2 of 
the former, to i of the latter. 

The phosphoric acid of the urine is derived partly from 
the food and, apparently, partly from the decomposition 
products of phosphorus-containing organic substances such 
as nuclein and lecithin. 

The average quantity of phosphoric acid in the twenty- 
four-hour urine, calculated as phosphoric anhydride (P2O.), 
is from 2.5 to 3.5 grams. This quantity is subject to much 
variation in health, and on a diet rich in earthy salts may 
fall to only a fraction of a gram, owing to the fact that the 
phosphoric acid combines with the earthy salts, and is thus 
prevented from being absorbed. 

Clinical Significance. — Under pathologic conditions the 
phosphoric acid is largely increased in the urine in ex- 
tensive diseases of the bones, as rickets, osteomalacia, dif- 
fuse periostosis, etc.; in destructive diseases of the lung, as 
in pulmonary tuberculosis, particularly in the early stages ; 
in extensive diseases of the nervous tissue, diseases of the 
brain, in chorea, etc. ; in acute yellow atrophy of the liver ; 
after sleep produced by potassium bromide, or chloral hy- 
drate (Mendel) ; and it is temporarily increased after copious 
drafts of water. 

Phosphoric acid is diminished in acute diseases, probably 
because only a small amount of food is taken ; and most of 
the chronic diseases, excepting those previously mentioned ; 
in all diseases of the kidney ; in gout ; in pregnancy, prob- 
ably due to the formation of the fetal bones ; and also after 
large doses of chalk, ether, or alcohol. 

The term phosphaturia should be restricted to indicate 
a constant increase in the total quantity of phosphoric acid 



PHOSPHATES. 109 

in solution in the urine. The term is frequently incorrectly 
applied to urine that has, constantly, a deposit of amor- 
phous or cr^^stalline phosphates. Those pathologic con- 
ditions in which the urine contains an abnormally large 
excess of phosphates in the twenty-four-hour urine may be 
said to be attended with ''phosphaturia." 

A condition of so-called phosphatic diabetes has been 
described by a few writers, in which the urine is free from 
sugar, but contains a continued large excess of phosphates. 
The symptoms are not unlike those of diabetes : /. e., large 
daily quantity of urine, emaciation, aching pains in the 
lumbar region, morbid appetite, dry, harsh skin, etc. Not 
infrequently this condition seems to alternate with diabetes 
mellitus : that is, the symptoms of diabetes continuing, the 
sugar disappears from the urine, and is apparently re- 
placed by a very large excess of the phosphoric acid — as 
much as lo grams. If the sugar reappears, the quantity 
of phosphoric acid falls to normal or even below the 
normal. 

Detection. — i. Earthy Phosphates. — The following 
test serves for the detection and approximate estimation of 
the earthy phosphates : Take a half test-tube of filtered 
urine, and add sufficient ammonic hydrate to render it 
alkaline. Upon warming the mixture the earthy phosphates 
separate, and soon begin to settle at the bottom of the 
tube. If, after eighteen to twenty-four hours, the deposit 
thus formed is from J^^ to ^ of an inch deep, the relative 
proportion may be said to be within normal limits ; if less 
than y^ of an inch, diminished ; and if more than ^ of an 
inch, increased. 

2. Alkaline Phosphates. — The following test may be 
applied for the detection and approximate estimation of the 
alkaline phosphates : After having separated the earthy 
phosphates as directed, the mixture is filtered. Take the 
entire filtrate in another test-tube, and add about one finger- 
breadth of magnesia mixture. ^ Upon warming the mixture 
a white precipitate, representing the alkaline phosphates, 
occurs, which, if normal, settles down to between ^ and 
^ of an inch after eighteen to twenty -four hours ; if less 
than ^ of an inch, diminished ; and if more than ^ of an 
inch, increased. 

^Magnesia Mixture. — Magnesium sulphate, ammonic hydrate, am- 
monium chloride, of each, I part ; water, 8 parts. 



110 INORGANIC CONSTITUENTS OF NORMAL URINE. 

Determination of Total Phosphoric Acid. — The follow- 
ing test is based upon the facts that (i) when a solution of a 
phosphate acidulated with acetic acid is treated with a solu- 
tion of uranium nitrate or acetate, a precipitate falls that is 
composed of uranium phosphate ; (2) when a soluble salt 
of uranium is added to a solution of potassium ferrocyanide, 
a reddish-brown precipitate, or color, is developed. 

Prepare the following solutions : 

(a) A Standard Solution of Uranmm Nitrate or Acetate. — 
Dissolve exactly 35.5 grams of pure uranium nitrate or ace- 
tate in distilled water sufficient to make looo c.c; i ex. 
of this solution corresponds to 0.005 gram of phosphoric 
anhydride (Pp^). 

Oftentimes it is not safe to use these salts of uranium, 
since they are frequently contaminated with uranic oxides. 
It then becomes necessary to prepare the standard solution 
in the following manner : 

1 . Make a standard solution of sodium phosphate by dis- 
solving 10.085 grams of the well-crystallized salt in dis- 
tilled water, and dilute to a liter; 50 c.c. then contain o.i 
gram of Pp,. 

2. To prepare the uranium acetate or nitrate solution, 
dissolve 20.3 grams of yellow uranic oxide in pure strong 
acetic acid to make the acetate, or in pure concentrated 
nitric acid to make the nitrate, and dilute with distilled water 
to nearly a liter. To determine the strength of this solu- 
tion, take 50 c.c. of the standard solution of sodium phos- 
phate in a glass evaporating dish, add 5 c.c. of the sodium 
acetate solution (given below), and proceed exactly as with 
urine (process, see below). The quantity of uranium solu- 
tion used is then read off, being that which is necessary to 
decompose the sodium phosphate, corresponding to o.i 
gram of P<,Og. Then calculate the amount of distilled 
water to be added to make i c.c. correspond to 0.005 gram 
of phosphoric anhydride. 

{b) Acid Sohition of Sodium Acetate. — Dissolve 100 
grams of sodium acetate in 800 c.c. of distilled water ; add 
100 c.c. of 30 per cent, acetic acid, and finally dilute with 
distilled water to 1000 c.c. 

(c) A saturated solution of potassium ferrocyanide, to be 
used as an indicator. 

Process. — Take 50 c.c. of the urine in a glass evapo- 
rating dish, add 5 c.c. of the sodium acetate solution, and 



PHOSPHATES. Ill 

heat the mixture to 80° C. over a water-bath. From a 
burette, run into the hot urine, drop by drop, the standard 
solution of uranium, as long as a precipitate forms or until 
a drop of the mixture, removed by means of a glass rod 
and placed on a porcelain plate or slab, gives a distinct 
brown color with a drop of the potassium ferrocyanide solu- 
tion. When this point is reached, the quantity of uranium 
solution used from the burette is read off. The number of 
cubic centimeters used multiplied by 0.005 will give the 
quantity of phosphoric acid (calculated-as phosphoric anhy- 
dride) in 50 c.c. of urine, and from this is calculated the 
quantity in twenty-four hours. 

The reddish-brown color which takes place with the 
solution of potassium ferrocyanide and the mixture, first 
makes its appearance at the time when the uranium solution 
has precipitated all of the phosphoric acid, and the mixture 
contains free uranium. 

Cochineal tmcture is highly recommended by Malot and 
Mercier as an indicator, instead of the potassium ferro- 
cyanide. The tincture is prepared by digesting a few grams 
of cochineal with a 250-c.c. mixture of one part of alcohol 
and three or four parts of water, in the cold. After several 
hours the solution is filtered and it is then ready for use. In 
the phosphoric acid test a few drops of this tincture are 
added to the urine, or phosphate solution, in the evaporat- 
ing dish ; the heat is then applied, and the standard uranium 
solution added until a faint but distinct permanent green 
color appears. The green color begins to appear as soon 
as there is the slightest excess of uranium in the solution — 
in other words, as soon as the phosphoric acid has been 
entirely precipitated. 

Quantitative Estimation of Phosphoric Acid Com- 
bined with Calcium and Magnesium (Earthy Phos- 
phates). — Process. — Take 200 c.c. of urine, precipitate 
with ammonic hydrate with the aid of gentle heat, allow 
to stand from twelve to twenty-four hours, then filter and 
wash with ammonia water. The filter-paper is then pierced 
at the point and the precipitate washed through into a 
beaker with a stream of hot water, and dissolved while warm 
in as little acetic acid as possible. Add 5 c.c. of the 
sodium acetate solution, dilute to 50 c.c, and proceed as 
previously indicated. The difference between the total 
amount of phosphoric acid and that in combination with 



112 INORGANIC CONSTITUENTS OF NORMAL URINE. 

calcium and magnesium — earthy phosphates — also repre- 
sents the quantity combined with the alkalies — alkaline 
phosphates. 

Purdy's Centrifugal Method for Total Phosphoric 
Acid. — Fill the percentage tubes to the lo-c.c. mark with 
the urine to be tested, and add magnesia mixture (formula, 
see p. 109) to the 15-c.c. mark. The tubes are then closed 
and inverted several times, until the urine and reagent are 
thoroughly mixed. The tubes are next placed in the cen- 
trifuge and revolved for three successive periods of five 
minutes each at the rate of 1000 revolutions a minute. 
The volume percentage is then read off In normal urine 
this will be found to be in the neighborhood of 8 per cent. 

The author has obtained, from a large number of obser- 
vations, a standard of percentage by lueight, by a com- 
parison of the volume percentages with the volumetric 
determinations. He has found that each ^ of a c.c. of 
precipitate calculated as P^O. is equivalent to 0.0225 per 
cent, by weight. 

SULPHATES, 

Sulphuric acid is present in the urine in two forms — as 
ordinary alkaline sulphates of potassium and sodium (pre- 
formed sulphuric acid), and as ethereal sulphates ^ (conjugate 
sulphuric acid). The sulphates are derived partly from the 
food and partly from the chemic changes of proteids in the 
tissues. The albuminous substances taken as food contain 
sulphur, which becomes oxidized in the economy and re- 
sults in sulphuric acid, some of which, in turn, immediately 
combines with a portion of the sodium and potassium to 
form ordinary sulphates, and a small portion to form the 
ethereal sulphates by pairing. 

The total quantity of sulphuric acid in the twenty-four- 
hour amount of urine of an adult taking a mixed diet is 
from 1.5 to 3 grams, or an average of 2 grams. About 
one-tenth of the total sulphuric acid is in the form of ethe- 
real sulphates. The quantity of sulphuric acid is subject 
to considerable variation, being largely dependent upon the 
amount of proteid food ingested. 

The sulphates are never found in the urine as a deposit, 
owing to the fact that they are very soluble compounds. 

^ See p. 84. 



SULPHATES. 113 

Clinical Significance. — The sulphates are increased in 
acute fevers, probably due to the markedly increased met- 
abolism. According to Bence Jones, they are especially 
increased in acute inflammatory diseases of the brain and 
spinal cord and in delirium. 

The sulphates are diininisJicd in all diseases, especially 
the chronic forms, and during the convalescent stage of 
acute diseases, when the metabolism and appetite are much 
diminished. They are notably diminished in cases of car- 
bolic acid poisoning, or following the internal or external 
use of large amounts of any phenol compound, such as 
salol, lysol, etc ; under such circumstances, however, the 
diminution of the ordinary sulphates is attended with a 
corresponding increase of the ethereal sulphates (phenol - 
potassium sulphate). 

In general, it may be stated that the variation in the 
quantity of ordinary sulphates eliminated in the urine runs 
parallel to that of urea. 

Detection. — The following test serves for both the de- 
tection and approximate estimation : Take one-half test-tube 
of filtered urine and add from one to two fingerbreadths 
of barium solution.^ A white precipitate occurs which, if it 
fills one-half the concavity of the test-tube in from eighteen 
to twenty-four hours, may be considered normal in quantity ; 
if less than one-half the concavity, diminished ; and if more 
than one-half the concavity, increased. 

Quantitative Determination. — i. Total Sulphuric 
Acid. — For the determination of the total amount of sul- 
phuric acid (SO3) — i. e., preformed and conjugate sulphuric 
acid together — one of two methods is adopted : {a) Gravi- 
metric method and (b) volumetric method. 

[a) Gravimetric Method. — This method consists in weighing 
the precipitate of barium sulphate obtained by adding barium 
chloride to a known volume of urine ; 100 parts of sulphate 
of barium correspond to 34.33 parts of sulphuric acid (SO3). 

Method {Salkowski). — Take 100 c.c. of urine in. a beaker, 
and acidulate with 5 c.c. of pure hydrochloric acid. This 
mixture is then boiled, and chloride of barium added to the 
boiling fluid until no more precipitate occurs. 

The precipitate is collected on a small filter of known 
ash, and washed with hot distilled water until no more 

^ Baruim Solution. — Barium chloride, 4 parts ; concentrated hydrochloric 
acid, I part; distilled water, 16 parts. 

8 



114 INORGANIC CONSTITUENTS OF NORMAL URINE. 

barium chloride occurs in the filtrate : /. c, until the filtrate 
remains clear after the addition of a few drops of sul- 
phuric acid. Then wash with hot alcohol and afterward 
with ether. Remove the filter, and place it with its contents 
in a platinum crucible. Heat to redness. Cool over sul- 
phuric acid in an exsiccator ; weigh, and deduct the weight 
of the crucible and filter ash. The remainder is the weight 
of barium sulphate formed, from which the SO3 is calcu- 
lated — 100 parts of barium sulphate corresponding to 34.33 
parts of SO3. 

Correction. — When the experiment is carried out as above, 
there is a slight error from the formation of a small quan- 
tity of sulphide of barium. This may be corrected as fol- 
lows : After the platinum crucible has cooled, add a few 
drops of pure sulphuric acid, which converts into a sulphate 
any sulphide present. The contents of the crucible are 
again heated to redness to drive off any excess of sulphuric 
acid, cooled and dried over sulphuric acid, and weighed. 

(p) Volumetric Method. — This process is conducted by 
adding a standard solution of barium chloride to a given 
quantity of urine as long as a precipitate occurs. 

The following solutions are necessary : 

1. A standard solution of barium chloride made by dis- 
solving 30.54 grams of pure crystallized barium chloride in 
water, and diluting to exactly one liter ; i cubic centimeter 
corresponds to 0.010 gram of SO,. 

2. An aqueous solution of potassium sulphate so made 
that one liter will contain 21.775 grams of the salt. 

Process. — Place 50 c.c. of the urine in a flask or small 
beaker, and add from 5 to 10 c.c. of pure hydrochloric 
acid. The mixture is then boiled over a free flame for fif- 
teen minutes, or heated on a water-bath for one hour. To 
the hot fluid the standard barium chloride solution is added, 
I c.c. at a time, until a precipitate fails to occur. After 5 
to 8 c.c. of the standard solution have been added, filter a 
small portion of the mixture through a very small filter- 
paper, and to the filtrate add a few drops of the standard 
solution. If a precipitate occurs, return the whole to the 
flask, add more barium solution, and test as before. Con- 
tinue until no more precipitate is formed on the addition of 
the barium chloride solution. Any excess of barium (that 
uncombined with sulphuric acid) is shown by placing a drop 
or two of the filtrate on a glass plate over a dark back- 



SULPHATES. 115 

ground, and adding a drop or two of the solution of potas- 
sium sulphate, when a decided cloudiness appears. This 
excess of barium must be avoided, and, therefore, in the 
test with potassium sulphate only the slightest cloudiness 
should appear, which shows that just the right amount of 
barium has been added ; if an excess of barium is present, 
the entire analysis must be repeated. 

The quantity of sulphuric acid is calculated from the 
amount of barium chloride solution used — one cubic centi- 
meter of which corresponds to o.oio gram of SO3. 

2. Conjugate Sulphuric Acid (Ethereal Sulphates). — 
Salkowski s Method. — One hundred cubic centimeters of 
clear, filtered urine are mixed with lOO c.c. of an alkaline 
solution of barium chloride (saturated solution of barium 
chloride, i part ; and a saturated solution of barium hydrate, 
2 parts, both saturated in the cold), the mixture being 
thoroughly stirred. After a few minutes this is filtered 
through a dry filter into a dry graduate up to the loo-c.c. 
mark. This portion, corresponding to 50 c.c. of urine, is 
now strongly acidulated with 10 c.c. of hydrochloric acid, 
boiled, kept at 100° C. on the water-bath for an hour, and 
then allowed to stand until the precipitate has completely 
settled : if possible, it should remain undisturbed for twenty- 
four hours. The further treatment of this precipitate (con- 
jugate sulphates) is then carried out as in the above- 
described gravimetric process. (See (a).) 

Calculations. — The molecular weight of BaSO^ being 
232.82 ; that of SO3, 79.86 ; of H^SO,, 97.82 ; and of S, 
32, the figure expressing the amount of H2SO4, SO3, or S, 
corresponding to i gram of BaSO^, is found according to 
the following equations : 

232.82 : 79.86 : : I : x, and x = 0.34301. . •. I gram of BaSO^ = 0.34301 

gram of SO3. 
232.82 : 97.82 : : I : x, and x = 0.42015. .*. I gram of 6380^ = 0.42015 

gram of HgSO^. 
232.82 : 32 : : I : X, and jf = 0,13744. .". I gram of BaSO^ = 0.13744 

gram of S. 

To calculate results, it is only necessary to multiply the 
weight of BaSO^ found by 0.34301, 0.42015, or 0.13744, 
in order to ascertain the amount of sulphuric acid contained 
in 50 c.c. of urine in terms of SO3, H2S0^, or S, respectively. 
This method of calculation applies to the gravimetric esti- 



116 INORGANIC CONSTITUENTS OF NORMAL URINE. 

mation of both the total sulphates and the combined sul- 
phates. 

To obtain the amount of preformed sulphuric acid, or 
that in combination with the alkalies, subtract the amount 
of combined SO3 from the total amount of SO3. The dif- 
ference is the preformed SO3. 

Example : One hundred cubic centimeters of urine gave 
0.5 gram of total barium sulphate. Then 0.5 multiplied by 
0.34301 ^0.171 gram of total SO3. Another 100 c.c. of 
the same urine gave 0.05 gram of barium sulphate from the 
ethereal sulphates ; then 0.05 multiplied by 0.34301 = 
0.017 gram of combined SO3. The difference between the 
total and the combined 503 = 0.171 — 0.017 = 0.154 
gram of SO3 in combination with the alkalies. 



CARBONATES. 

A freshly passed urine of alkaline reaction generally con- 
tains small quantities of carbonates and bicarbonates of 
sodium, magnesium, calcium, and ammonium, all of which 
arise in the economy from the carbonates of the food, or 
from salts of mahc, tartaric, lactic, succinic, and other vegeta- 
ble acids ingested with the food. They are, therefore, most 
abundant in the urine of herbivora, whose urine is thus 
rendered alkaline. A urine containing carbonates is either 
turbid when passed, or soon becomes so on standing. The 
deposit, if allowed to settle, will, on examination, be found 
to consist of calcium carbonate mixed with phosphates. 

According to Wurster and Schmidt,^ a liter of normal 
human urine of a specific gravity of 1020, if acid in reac- 
tion, contains, on an average, from 40 to 50 c.c, and if 
neutral or alkaline, over 100 c.c. of carbonic acid, which is 
capable of being expelled by a current of air. The amount 
of carbonic acid per 100 c.c. varies between 17 c.c. (urine 
of low specific gravity) and 294 c.c. (urine of high specific 
gravity). 

Carbonic acid forms neutral (normal) and acid salts. Of 
the alkaline carbonates, both the acid and the normal are 
soluble, but the acid is considerably less soluble than the 
normal. The normal carbonates of calcium and magnesium, 
on the other hand, are very slightly soluble, but the acid is 

1 "Centralbl. f. Physiologic," 1887, 421. 



IRON.— HYDROGEN PEROXIDE. 117 

more soluble than the normal. The carbonate of ammo- 
nium is volatile at ordinary temperature. 

For the detection and quantitative determination of car- 
bonic acid, both free and combined, see Neubauer and 
Vogel, ''Analyse des Harns," Bd. i, 1898, S. 37 u. 735. 



IRON. 

Iron is found only in minute traces in the residue of the 
urine after ignition. According to Magnier, the amount of 
iron in a healthy man of medium weight varies between 0.003 
and 0.0 1 1 gram in a liter. The coloring-matter, which is 
precipitated with the uric acid on the addition of concen- 
trated hydrochloric acid, according to Kunkel, contains 
iron. 

Detection. — The ash of the residue of urine is always 
used for the isolation and detection of iron. It is dissolved 
in a little hydrochloric acid, and the solution divided into 
two parts. The first part is boiled with a drop of nitric 
acid and treated with a solution of potassium sulphocyanide 
which, if ferric oxide be present, produces a red or blood- 
red color. If potassium ferrocyanide is added to the other 
half of the solution, after boiling with nitric acid and dilut- 
ing, flocculi of Prussian blue separate after standing a time. 

For the quantitative determination of iron and further 
information regarding this substance the reader is referred 
to Neubauer and Vogel, " Analyse des Harns," Bd. i, 
1898, S. 47 u. 750. 

HYDROGEN PEROXIDE. 

This substance was first detected in the urine by Schonbein. 1 
The most reliable reaction that serves for its recognition depends 
upon the power it possesses of bleaching a dilute tincture of 
indigo. The urine to be tested must be perfectly fresh. 

The relative unimportance of this substance in the urine for- 
bids more than a mere mention here. ^ 

1 " Journ. f. prakt. Ch.," xcn, 168, 1864. 

2 See Neubauer and Vogel, "Analyse des Harns," 1898, S. 39. 



118 URINARY CRYOSCOPY. 



URINARY CRYOSCOPY. 

The determination of the freezing-point of urine, which 
was first studied and used by Bouchard in 1870, has re- 
ceived special attention during the past two years. It is 
dependent on Raoult's law — i.e.: "One molecule of any 
compound, when dissolved in one hundred molecules of a 
liquid, lowers the freezing-point of the liquid by an amount 
which is nearly constant." 

The freezing-point of the urine is normally from — 1.30° 
to — 2.20° C. Special apparatus and a thermometer regis- 
tering from y-l-Q- to y-oVo" degree are necessary for an 
accurate determination. The following data are required : 
(i) the freezing-point of the urine; (2) the percentage of 
sodium chloride ; (3) the twenty-four-hour quantity of urine; 
(4) the weight of the person in kilos ; and (5) the total 
solids of the urine calculated from the specific gravity (see 
page 40). 

The ratio of the freezing-point of the urine to the per- 
centage of sodium chloride sometimes furnishes information 
of value in the diagnosis of heart disease and chronic 
nephritis. The subject requires further investigation before 
much of practical value can be ascribed to it. 

(For further information see Archiv f. exp. Path. u. 
PJiarinacologie, v, 29, 5303; ZeitscJnift f. klin. Me dicing 
1900, Bd. 65, S. i; Physical Reviezv, 1893, 1896, 1897, 
and 1 901; Munch, vied. Wochenschr., Oct. 30, 1900; 
Philadelphia Medical Journal, June 29, 1901.) 



CHAPTER IV. 
ABNORMAL CONSTITUENTS OF URINE. 

PROTEIDS. 

Under pathologic conditions urine may contain a number 
of proteids — /. ^., serum albumin, serum (or para-) globulin, 
albumose, peptone (?), hemoglobin and methemoglobin, and 
fibrin and fibrinogen. Egg-albumin is occasionally found, 
especially after the liberal ingestion of eggs as a food. 
Several of these proteids may be present in the urine at the 
same time, or, on the other hand, only a limited number 
present, such as albumin and globulin, albumin and hemo- 
globin, etc. 

General Reactions of the Proteids. 
A. Color tests. 

1. Xanthoproteic Reaction. — Heat the solution of the 
proteid with concentrated nitric acid. There results a yellow 
color, which, on the addition of an alkaline hydrate, changes 
to a deep orange. If much proteid, except albumose and pep- 
tone, be present, a yellow precipitate is obtained at the same 
time ; with less proteid, its solution merely turns yellow on 
boiling, and orange on the addition of an alkali ; if only a trace 
is present, no yellow color is observed until after the addition 
of the alkali. 

2. Millon's Reaction. — With Millon's reagent ^ proteids, 
when present in sufficient quantity, give a precipitate that turns 
red on heating. If only present in traces, no precipitate is ob- 
served on heating, but merely a red colorization of the solution. 

3.~ Piotrowski's Reaction. — If a solution of the proteid be 
mixed with an excess of a concentrated solution of sodic hy- 
drate, and one or two drops of a dilute solution of sulphate of 
copper be added, a violet color is obtained, which deepens on 
boiling. Alburaoses and peptones give a rose-red color (Jniiret 
reaction') ; care must be taken in the addition of the cupric 
sulphate solution, since an excess gives a reddish-violet color 

1 See foot-note, p. 170. 
119 



120 ABNORMAL CONSTITUENTS OF URINE. 

somewhat similar to that obtained in the presence of other pro- 
teids. 

The foregoing tests serve to detect the smallest traces of pro- 
teids. 

B. General Precipitants. — Solutions of proteids are pre- 
cipitated by the following reagents (peptones are exceptions 
in most cases) : 

1. Render the solution strongly acid with acetic acid, and 
add a few drops of a solution of potassium ferrocyanide. A 
precipitate shows the presence of proteids, except true peptone 
and some forms of albumose. 

2. Render the fluid as before strongly acid with acetic acid, 
add an equal volume of concentrated solution of sodium sul- 
phate, and boil. A precipitate forms if proteids, except pep- 
tone, are present. This test is particularly useful, since the 
reagents used do not produce any decomposition of other 
substances that may be present, and do not interfere with cer- 
tain other tests that may be applied after the removal of the 
proteids by filtration. 

3. Completely saturate the fluid with ammonium sulphate, 
having previously neutralized and then rendered /^/;2//v acid with 
acetic acid ; this precipitates all proteids except peptones. 

4. Alcohol, tannic acid, phosphotungstic acid, and potassio- 
mercuric iodide are also general precipitants, the last two being 
particularly useful for delicate tests. 

The term " albumin," in its ordinary clinical use, includes 
not only serum albumin, but also serum globulin, and, in 
rare instances, albumose. It should be remembered that 
these proteids differ in many respects, and, so far as is pos- 
sible, should be separately identified. 



ALBUMIN. 

Serum albumin is doubtless the most important proteid 
found in the urine. It can safely be considered an abnor- 
mal constituent when present in amounts capable of being 
detected by the tests that are ordinarily used. Whether 
or not albumin is present in minute traces in the urine in 
health — such traces being incapable of detection by the 
tests generally employed — is still a debated question. From 
a practical point of view this question can be disregarded. 

Albuminuria is not necessarily an indication of renal dis- 
ease, for albumin may be present in the urine without the 
slightest alteration in the renal structure. In general, the 
presence of albumin indicates a disturbance or disease in 



ALBUMIN. 121 

some part of the genito-urinary tract, and with one exception 
— /. €., "■ functional albuminuria" — is always accompanied 
by formed physiologic or pathologic elements in the urinary 
sediment. 

Albumin is not capable of crystallization ; it is soluble in 
water, in dilute saline solutions, and in saturated solutions 
of sodium chloride and magnesium sulphate. It is, how- 
ever, precipitated by saturating with sodium or ammonium 
sulphate. It is coagulated by heat, usually at from 70° to 
73° C., particularly in the presence of sodium chloride. It 
is not precipitated by ether, in which respect it differs from 
egg-albumin. Under ordinary conditions it does not pass 
through animal membranes. 

Causes of Albuminuria. — In general, the causes of 
albumin in the urine are : (i) Changes in the kidney structure, 
which, on account of its abnormal state, allows the albumin 
to transude ; (2) alterations in the blood pressure in the 
kidneys ; (3) abnormal changes in the quality of the 
blood entering the kidney, thus rendering its serum albu- 
min more diffusible ; and (4) disturbances or diseases of 
the urinary tract below the kidneys — /. ^., renal pelvis, 
ureters, bladder, prostate gland, and urethra. Under this 
heading may be included, also, albuminous elements enter- 
ing from the genital tract. 

Clinical Importance. — i. Albuminuria due to patho- 
logic changes — inflammatory and degenerative — in the 
kidneys is without doubt the most important, and often the 
most serious, form. These changes include the variety of 
diseases commonly grouped under the term of Bright' s 
disease. Not only do we have to deal with these extensive 
diseases of the kidney, but also with certain disturbances 
of the renal function that are accompanied by the pres- 
ence of albumin. 

The quantity of albumin in the urine in various renal af- 
fections may vary between the slightest possible trace and 
from three to four per cent. From the quantity of albumin 
alone it is impossible to judge in all cases of the nature or 
severity of the renal changes. For instance, the grave con- 
dition — chronic interstitial nephritis — may exist with only 
the slightest possible trace of albumin in the urine. On the 
other hand, a simple renal congestion may, for a short 
time, be accompanied by from ^ to i^ of one per cent, of 
albumin. In certain conditions — for example, an acute 



122 ABNORMAL CONSTITUENTS OF URINE. 

nephritis in which the diagnosis has already been estab- 
lished — very general information concerning the progress 
of the disease may be gained by examining the urine daily 
for albumin. Such information, however, is unsafe if not 
accompanied by a complete chemic and microscopic exam- 
ination of the tzuenty-foiir-lwiir secretion. 

2. The second form — alterations in the blood pressure 
in the kidneys — is a common cause of albuminuria. It is 
always the result of circulatory disturbances that include 
the renal vessels. There is usually more or less structural 
change in the kidneys, and, besides albuminuria, a greater 
or smaller number of formed pathologic elements in the 
sediment. There may be an increase in the arterial pres- 
sure, as in certain affections of the nervous system in which 
there is an interference with the vasomotor regulation of the 
coats of the blood-vessels ; also in sudden exposure to cold 
and wet, in which case the internal organs become ab- 
normally filled with blood ; and in arteriosclerosis. On 
the other hand, the blood pressure may be diminished, as 
in certain forms of cardiac disease, which results in a back 
pressure in the renal veins (passive congestion), and hence 
albuminuria. The pressure of tumors or of the pregnant 
uterus on the abdominal veins will often cause albuminuria, 
but soon after the cause is removed the albumin disappears 
from the urine. 

So-called " Functional or Physiologic Albuminuria." 
— The most marked condition in which this occurs is after 
prolonged muscular exertion. A study of this condition 
was made by Leube,^ who found albumin in the urine in i6 
per cent, of soldiers after a prolonged march; Oertels^ found 
it in 3 per cent, of the cases examined. 

3. This form, which causes albuminuria by changes in 
the quality of the blood entering the kidney, is notably 
seen in cases of anemia (this is perhaps partially explained by 
the lessened nutrition of the renal cells), and in the first stage 
of the convalescence from cholera. In phosphorus-poison- 
ing and hemoglobinemia, also in carbon monoxide poison- 
ing and after the excessive use of morphine, the blood 
is probably so altered as to permit the transudation of the 
serum albumin into the renal tubules. In some of these 

1 " Virchow's archiv," Lxxii, 145 ; LXXix. 

2 <' Ziemssen's Handbuch der allgemein. Therapie," iv. 



ALBUMIN. 123 

cases of poisoning the kidneys are simultaneously affected, 
so that the cause of the albuminuria may be partly ex- 
plained by the renal disturbance. 

4. This form of albuminuria has been variously termed 
false, adventitious, or accidental. Under this class are in- 
cluded a large number of urines that contain comparatively 
small amounts of albumin. The quantity of albumin usually 
depends upon the amount of blood and pus coming from 
the diseased area, and, therefore, may be abundant if much 
blood is present. In many instances, particularly when the 
disturbance or disease is located in the bladder or urethra, 
the kidney is not affected at all by the condition, the urine 
being normal until it reaches the affected area. On the 
other hand, in cases of pyelitis and prostatitis, the function 
of the kidneys is very apt to be secondarily disturbed by 
the local disease, and consequently more or less albumin 
of renal origin. Albumin not infrequently gets into the 
urine from the genital tract : in the female, from the vagi- 
nal discharge, consisting of a mixture of more or less pus, 
blood, and epithelium, also, occasionally, menstrual fluid ; 
in the male, from seminal fluid. As a rule, the source of 
albumin in such cases may be determined by both chemic 
and microscopic investigation, together with the local symp- 
toms. It is important that this variety of albuminuria be 
borne in mind by the student in order to avoid error. 

Albuminuria of Adolescence and Cyclic Albumin- 
uria. — These forms may, or may not, be accompanied 
by a renal disturbance : in other words, renal casts and 
cells may or may not be present in the sediment. A 
large proportion of these cases occurs in youths and young 
adults. The quantity of albumin usually varies between a 
slightest possible trace and one -half of one per cent., gener- 
ally averaging one-eighth of one per cent., or less. The 
quantity often varies as the time of day — /. e., being less (or 
sometimes absent) at night during the hours of rest, appear- 
ing in the morning, especially upon exercising, increasing 
during the day, and diminishing toward evening. In some 
of these cases the amount of albumin is fairly constant, day 
and night, particularly in cases of albuminuria of adoles- 
cence. The presence of albumin may continue for weeks, 
months, or even years, and then finally disappear. Little 
can be said concerning the causes of these forms of albu- 
minuria. There are often circulatory changes that appear 



124 



ABNORMAL C0X5TITUEXTS OF URIXE. 



to be functional in character, and the individual is generally 
found to be somewhat below the standard of vigorous 
health. An abnormal increase in the blood pressure or 
changes in the quality of the blood have been suggested as 
the possible explanation of this form of albuminuria. 

It is safe to conclude from the foregoing consideration 
that the presence of albumin in the urine is to be regarded 
merely as a *' danger signal," and that when it is present, a 
further chemic and microscopic study of the urine is neces- 
sar^' before deciding as to the existing condition. Albu- 
minuria in itself can not be considered diagnostic. 

Detection of Albumin in Urine. — Nitric Acid Test. 
— Always filter the urine to be tested. This is an important 
step, even though the urine appears 
to be perfectly clear, since all urines 
contain a certain amount of sus- 
pended matter, which must be re- 
moved in order to detect the smallest 
traces of albumin. 

Take a perfectly clear and dr\' wine- 
glass (Fig. 13),^ and one-half fill with 
the filtered urine. Incline the glass 
so that the urine reaches nearly the 
edge, and then underlie ivith concen- 
trated nitric acid (C. P.), pouring it 
from the bottle as slowly as possible 
(Fig. 14), until the acid equals ap- 
proximately one-third the volume of 
urine used. If albumin be present, a 
more or less distinct white band or 
zone of coagulated albumin will be 
seen just above the junction of the 
acid and urine. This zone will var}' in thickness according 
to the quantity of albumin present, the rapidity with which 
the acid is poured, or, in other words, the extent to which 
the acid and urine are mixed, and, lastly, the amount of 
effervescence that follows the addition of acid (decomposi- 
tion of carbonate, and in case }'ellow nitric acid is used, the 
decomposition of the urea and uric acid, with efTer\-escence). 




Fig. 13. — Wine-glass (one 
half actual size). 



^ The wine-glass here represented is perhaps best suited for the satisfactory 
performance of the nitric acid test. It is made of clear white glass, and is 
free from defects. It was formerly manufactured by the Sandwich Glass Co., 
under the name of " Collamore Wine Glass." 



ALBUMIN. 



125 



Approximate Estimation of Albumin. — If in every case 
the proportion of urine and acid is as previously indicated, 
and the nitric acid is poured from the bottle as slowly as 
possible, much can be told concerning the approximate 
quantity of albumin present by the appearance of the zone 
obtained. It is very difficult, and, indeed, practically impos- 
sible, to give the percentage of albumin as judged from the 
zone, if the quantity is less than a trace ; if more than a 
trace, a general idea as to the percentage can be given. 

{ci) Slightest Possible Trace. — This is, naturally, the 
smallest amount of albumin capable of being detected by 
ordinary tests, and can certainly be considered an entity in 
connection with the nitric acid test. These slightest traces, 
I regret to say, are often overlooked, especially by the 
inexperienced, because the proper means for their detection 




Fig. 14. — Method of performing the nitric acid test for albumin. 



are not employed. It is important, first of all, that the 
wine-glass be perfectly clean, and, secondly, that a dark 
background be adjusted obliquely in front of, or a little 
to one side of, the glass, between the source of light and 
the glass, but not so placed as entirely to cut off the light. 
(See Fig. 15.) In this way the merest haze of albumin, 
which is usually a rather wide, hazy band, approximately 
-^ to ^ of an inch in width, and not a sharp and narrow 
band, is discernible. A clear, byt usually narrow, layer of 
clear urine can frequently be seen between this haze or 
cloud of albumin and the zone of acid urates that forms 
higher up in the layer of urine. The slightest possible 
trace can not be seen without the use of a dark back- 
ground. 



126 



ABNORMAL CONSTITUENTS OF URINE. 



ip) Very Slight Trace, — This is a faint zone which is best 
seen by using a dark background. If the wine-glass is 
held between the eye and the light, a very faint cloud 
may be seen, but the observer will often be in doubt as to 
the presence of albumin until a dark background is used. 
This zone can not be discerned as the observer looks down 
on to the surface of the urine : that is, the bottom of the 
wine-glass can be distinctly seen. 

(c) Slight Trace. — This is a distinct white zone which 
can readily be seen from the side without a dark back- 
ground. In looking through the urine from above down- 
ward, a very faint cloud can be made out, although the 
bottom of the wine-glass can be distinctly seen. 



\ ■ 


1 

1 '. 






^JpwgJIpMI 


\ 


CZ^'^lB'i 


M 


jiBB^T^" *"' '^^ 


1 


^^^^^^^^^^S.' "^ ^^^^^Q^BB^^Hfettii^^^^^^^^^^^^RIP 



Fig. 15. — Method for the detection of minute quantities of albumin, 
albumin ; upper zone, acid urates. 



Lower zone, 



(d) Trace. — A trace of albumin is a zone which is dis- 
tinctly seen without a dark background, when viewed from 
the side. In looking through the urine from above down- 
ward a decided cloud is seen, but this cloud is usually not 
so dense as to prevent one's seeing the bottom of the 
wine-glass. 

{e) Large Trace (including -^ of i per cent.). — A zone 
which, seen from the side, is very evident, but not granular 
(flocculent). When viewed from above downward, it is 
found to be quite dense, although not so dense as to 
obstruct entirely the transmission of a little light. (The 



ALBUMIN. 127 

light can be cut off by placing the hand between the source 
of light and the glass.) 

(/") One-eighth of One Per Cent. — A marked zone which 
is not flocculent. The bottom of the glass can not be 
seen, although a faint ray of light can usually be seen 
coming through the zone. 

(^g) One-fourth of One Per Cent. — A zone which is 
quite flocculent when viewed from the side. No light can 
be seen through the band in looking from above downward. 

(Ji) One-Jialf of One Per Cent, or More. — When the quan- 
tity of albumin reaches one-half of one per cent, or more, 
a dense, very flocculent band forms ; light can not be seen 
through it. Above one-half of one per cent, it is difficult 
to estimate the approximate quantity present ; a quantita- 
tive test should then be made according to the instructions 
given on page 131. 

If the proper appliances are at hand, it is advisable to 
make a quantitative determination of the albumin in all 
cases in which the amount is a trace or more. 

In the nitric acid test practically nothing can be deter- 
mined from the width of the zone of albumin. In dealing 
with the smaller quantities the width of the band will 
depend largely on the rapidity with which the nitric acid is 
poured, and also upon the amount of effervescence that 
follows the addition of the acid. The bands will usually 
vary in width from about 3^ of an inch to \ of an inch or 
more. Usually in the presence of the large quantities of 
albumin the band is quite narrow, but exceedingly dense. 

In the nitric acid test, when minute traces of albumin are 
present, the hazy band or cloud of albumin generally be- 
comes more intense after the lapse of one or two minutes. 

Heat Test. — The heat test for albumin depends upon 
the separation (coagulation) of this proteid from fluids which 
2iYQ faintly acid, preferably with acetic acid, by heating at a 
temperature of about 75° C. 

It is essential that the urine should have a faintly acid 
reaction ; for, if the urine is alkaline, the albumin is in the 
form of alkali albumin, which is not coagulable by heat. 
Again, if too strongly acidulated, the albumin is in the form 
of acid albumin, which is likewise incapable of being coagu- 
lated by heat. 

I. If the urine is acid, take one-half test-tube of the filtered 
urine, add one drop (not more) of 10 per cent, acetic acid, 
and mix thoroughly ; hold the test-tube by the lower portion, 



128 ABNORMAL CONSTITUENTS OF URINE. 

and boil the upper one-third of acidulated urine. If a cloud 
forms, it consists of either albumin or earthy phosphates. 
Add another drop or two of acetic acid, boil again, and if 
the cloud remains, albumin is present ; if the cloud disap- 
pears, the precipitate is phosphatic. 

2. If the urine is alkaline, take one-half test-tube of the 
filtered urine, add two or three drops of lo per cent, acetic 
acid, and boil the upper one-third of the urine as directed. 
If the urine has not yet been rendered faintly acid, a pre- 
cipitate or coagulum of albumin will not appear until 
sufficient acetic acid has been added, drop by drop, to 
the hot urine, to faintly acidulate. As soon as the proper 
reaction has been reached, a precipitate will appear if albumin 
be present. As stated previously, the further addition of one 
or tw^o drops of acetic acid will help to determine whether 
the precipitate is phosphatic or a coagulum of albumin. 

It scarcely ever happens that a urine, when voided, is 
too acid for the successful application of the heat test, and 
even in a strongly acid urine it is often necessary to use 
one drop of acetic acid in order that the examiner may be 
satisfied of the presence or absence of albumin. 

Nitric acid, which is often used for acidulation instead of 
acetic acid, is liable to lead to serious error in judging of 
the presence of albumin by the heat test. This is espe- 
cially so if the albumin is present in small amount, since 
the addition of so strong an acid converts the albumin to 
acid albumin, — syntonin, — which is soluble and not coag- 
ulated by boiling. Less danger exists in the use of acetic 
acid (lo per cent.), providing, however, that an excess of the 
acid is avoided. Nitric acid should, therefore, not be used 
in connection with the heat test. 

The approximate estimation of the quantity of albumin 
from the density of the coagulum of albumin by heat is not 
always a simple matter in the hands of most observers, 
since a standard for comparison can not be easily fixed. 
On the other hand, those who prefer to use the heat test 
instead of the nitric acid test for routine work can learn to 
estimate the approximate quantity in a general way. 

The Potassium Ferrocyanide and Acetic Acid Test. 
— This test may be applied in two ways : i. e., (a) by actual 
mixture and [b) by the contact method. 

(a) To a half test-tube of urine add from three to five 
cubic centimeters of a solution of potassium ferrocyanide 
(i : lo), and from one to three cubic centimeters of 50 per 



ALBUMIN. 129 

cent, acetic acid ; the reagents and urine should be thor- 
oughly mixed. If albumin be present, a white, finely divided 
precipitate will appear within half a minute or a minute. 

(/)) Take a mixture of one part of 50 per cent, acetic acid 
and two parts of potassium ferrocyanide solution in a wine- 
glass, and carefully overlay with the urine to be tested. If 
albumin be present, a narrow, sharply defined, white zone 
will appear just above the junction of the two fluids. The 
urine to be tested must be acid in reaction in order to 
obtain a satisfactory test. This reagent does not precipi- 
tate peptones, alkaloids, or phosphates, but may precipitate 
acid urates. It has been found to react slightly with 
artificial solutions of nucleo-albumin. 

A comparative experimental study of the three tests 
described convinces the writer of the following order 
of dehcacy : (i) nitric acid test; (2) heat test; (3) potas- 
sium ferrocyanide and acetic acid test. 

Other Tests for Albumin. — It has long been known 
that albumin is coagulated or precipitated by other agents 
than nitric acid, heat, and potassium ferrocyanide and acetic 
acid. Some of these tests have claimed much attention, 
and have been found to be extremely delicate, but it is safe 
to say that their delicacy is often at the expense of accuracy. 
The chief objection to many of the tests is that they pre- 
cipitate other substances than albumin, and although these 
substances are distinguished from albumin by taking certain 
precautions, or by the application of other tests, the ob- 
server is either misled, and considers that albumin is present, 
or he is left in a confused state of mind. While, doubtless, 
it is desirable that we should possess tests for albumin 
which are very sensitive, yet extreme delicacy of re- 
action is of secondary consideration and not of clinical 
importance. Such tests should, therefore, not enter into 
the routine examination of the urine, thus avoiding unneces- 
sary confusion. 

Picric Acid Test. — This test has been strongly advised by 
Dr. George Johnson. 1 The test is applied as follows: Into a 
test-tube six inches long pour a four-inch column of filtered 
urine. Then, holding the test-tube in a slanting position, pour 
gently an inch of a saturated solution of picric acid (made by 
adding six or seven grains of picric acid to a fluidounce of boil- 

^ "Albumin and Sugar-testing," London, 1884. 



130 ABNORMAL CONSTITUENTS OF URINE. 

ing distilled water) over the surface of the urine ; the reagent 
thus mixing with only the upper layer of the urine. As far as 
the yellow color of the reagent extends, the coagulated albumin 
renders the liquid turbid, contrasting with the clear urine below. 
In order to obtain a satisfactory reaction there must be an actual 
mixture and not a mere surface contact. When the quantity of 
albumin is small and the turbidity is slight, the application of 
heat to the upper part of the turbid mixture increases it. This 
reagent also precipitates urates, peptone, albumose, vegetable 
alkaloids, and mucin, all of which, except mucin, are dissolved 
by a degree of heat much below that of the boiling-point. 

The Potassio-mercuric-iodide Test. — This test was sug- 
gested by M. Charles Tanret. The reagent (double iodide of 
mercury and potassium, acidulated with acetic acid) is prepared 
as follows: Bichloride of mercury, 1.35 grams; potassium 
iodide, 3.32 grams; acetic acid, 20 c.c. ; distilled water, suf- 
ficient to make 100 c.c. The bichloride of mercury and the 
potassium iodide should be dissolved separately in water, and 
the two solutions mixed; the acetic acid is then added, and 
the whole mixture made up to 100 c.c. The contact method is 
used, and since the reagent is heavier than the urine, the latter 
is carefully poured on to the surface of the reagent in a test- 
tube or wine-glass. If albumin be present, a white, sharply de- 
fined band appears at the junction of the two fluids. This test 
precipitates the same substances as picric acid, including nucleo- 
albumin. All of these precipitates except albumin are dissolved 
by gentle heat, the precipitate reappearing upon being cooled. 
According to Oliver, the precipitate of nucleo-albumin is not 
dissolved by heat if a large excess of reagent is used, the mer- 
curic salt apparently preventing solution. This test is exceed- 
ingly delicate. 

Trichloracetic Acid Test. — This test is applied by means of 
the contact method. The reagent is prepared by dissolving 
15 grams of the crystals of trichloracetic acid in about 10 c.c. 
of distilled water, making a saturated solution. Delicate results 
are claimed for this test, but, from the fact that it precipitates 
mucin and nucleo-albumin, it can not be regarded as a reliable 
test for albumin. 

Sodium Tungstate. — This test was suggested by Dr. George 
Oliver as a very sensitive reagent for albumin. The reagent is 
prepared by mixing equal parts of a saturated solution of sodium 
tungstate (1:4) and a saturated solution of citric acid. The 
contact method is used, and since the reagent is heavier than 
urine, it is best applied by the overlaying method. The reagent 
precipitates, in addition to albumin, acid urates, peptone, and 
mucin. It gives no reaction with the alkaloids, and all precipi- 
tates, except albumin and mucin, are readily dissolved by heat. 



ALBUMIN. 131 

A large number of other so-called '' delicate tests " have been 
suggested for the detection of albumin, only a few of which are 
worthy of mention: Acidulated brine test (Roberts), nitric- 
magnesium test (Roberts), phenic acid test (Millard), Heiden- 
lang's test, Heynsius'stest, acetic acid and sodium sulphate, etc. 

Albumin-test Papers. — According to the suggestion of Dr. 
George Oliver, a number of the tests named have been prepared 
and used in paper form. This is accomplished by using chem- 
ically inert filter-paper, some of which is to be saturated with 
solutions of the albumin reagents, and some with citric acid, 
and then drying. The papers are then cut into slips of con- 
venient size for testing, and may be carried about in the pocket- 
case for use at the bedside of the patient. In testing, the follow- 
ing method is followed : Into a small test-tube containing 5 c.c. 
of distilled water are dropped a reagent paper and one charged 
with citric acid. After agitation for a minute or so the test- 
papers are removed, and the solution is ready for testing. The 
urine is now added ; the test may be conducted either by a mix- 
ture of the two or by the contact method, of which Dr. Oliver 
advises the latter. 

Dr. Oliver now recommends the use of two reagents only for 
albumin — viz. , the potassium ferrocyanide and potassio-mercuric- 
iodide papers. The former of these will be found trustworthy, 
and of very great convenience at the bedside. 

The potassio-mercuric-iodide test must, in all cases, be con- 
trolled by heating, otherwise it may be misleading. 

The Removal of Albumin by Heat. — If the urine to be 
examined contains more than a trace of albumin, it should 
be removed before testing for chlorides, sulphates, and 
sugar, since the albumin either enters into combination 
with the reagents or reacts with them in such a manner as 
to render the tests unreliable. The best method for the 
removal of albumin is to coagulate it by heat ; this should 
be applied in connection with both qualitative and quanti- 
tative analyses. 

1. For Qualitative Tests. — Take one-third of a test- 
tube of urine, add one drop of dilute acetic acid, and boil the 
whole mixture thoroughly. If a flocculent precipitate does 
not form, add at intervals, drop by drop, more acetic acid, 
heating the mixture after each addition until a distinct floc- 
culent coagulum forms. Filter ; the filtrate should be per- 
fectly clear and practically free from albumin. 

2. For Quantitative Analysis. — Take a definite 
quantity of the urine, say 50 c.c, place in a porcelain evap- 



132 ABNORMAL CONSTITUENTS OF URINE. 

orating dish, add two or three drops of dilute acetic acid, 
and boil thoroughly. If a flocculent coagulum of albumin 
does not appear, add a few more drops of the acetic acid, 
drop by drop, stirring constantly and continuing the heat 
until such a flocculent coagulum forms. Filter, — the filtrate 
should be free from precipitate, — and wash once or twice 
with water. Allow the filtrate and wash-water to run into 
a graduate, and add sufficient water to make the original 
volume (50 C.C.). Mix the contents of the graduate thor- 
oughly, and use for the quantitative tests. 

In removing albumin by heat a flocculent coagulum 
should be obtained in all cases, and this is accomplished 
when the urine has a faintly acid reaction (preferably with 
acetic acid). In case a flocculent coagulum is not obtained, 
the filtrate will be more or less turbid, the turbidity being 
due to the finely divided precipitate of albumin. Such a 
turbid filtrate is unfit for further tests. 

Quantitative Estimation of Albumin in Urine. — Ex- 
pression of Quantity of Albumin Found in Urine. — In 
referring to the quantity of albumin found in the urine the 
author, in all cases, means the quantity by weight, and not 
the bulk measure ; thus, if the expression "J^ of i per 
cent." be used, it is i^ of i per cent, by weight that is 
intended. We not infrequently read that urines contain 25, 
50, and even 75 per cent, of albumin. The quantity by 
bulk is, of course, intended, since 3 to 5 per cent, by 
weight is probably the maximum amount of albumin that 
urine can contain. Much greater care should be exercised 
in speaking of the quantity of albumin present, using the 
terms percentage by weight or percentage by bulk, according 
to the meaning of the writer. Attention given this matter 
will be the means of avoiding much confusion, particularly 
to students. 

The term *'i per mille," or "i p. m.," refers to the num- 
ber of grams of albumin contained in i liter of urine ; 
thus, the foregoing expression equals I gram of albumin in 
1000 c. c. of urine, or -^-^ of i per cent, by weight ; 2 p. m. 
equals 2 grams in looo c. c, or -f^ of i per cent. ; 5 p. m. 
equals 5 grams in 1000 c. c, or -1- of i per cent., etc. 

Gravimetric Process. — This process for the quantita- 
tive estimation of albumin gives accurate results, but is 
unsuitable for clinical purposes on account of the length of 
time and the apparatus required for its completion. 



ALBUMIN. 



133 




Take lOO c.c. of the urine, place in a beaker or glass 
evaporating dish, and heat on a water-bath. A two per 
cent, solution of acetic acid is then added, drop by drop, 
until, upon boiling, a flocculent precipitate of albumin 
separates. This is then filtered through an 
ash-free filter which has been previously- 
dried and weighed. The precipitate is 
washed successively with water, alcohol, 
and ether, and dried at a temperature of 
120° to 130° C. After cooling the filter 
is ao:ain weis^hed, and the difference in 
weight due to the precipitate represents the 
quantity of albumin in the 100 c.c. of 
urine used. 

Devoto^ recommends the following pro- 
cedure : Take a definite quantity of urine, 
precipitate the albumin with ammonium 
sulphate, heat on a water-bath, and wash 
the precipitate with boiling water until the 
filtrate no longer becomes cloudy on stand- 
ing, or upon the addition of sodium chloride. 
The precipitate is then washed with alcohol 
and ether, and the remainder of the process 
conducted as previously directed. 

Esbach's Method. — This test is made 
by means of a standard graduated glass 
tube or albuminometer,^ as shown in figure 
16. The process is as follows : The fol- 
lowing solution is prepared : Picric acid, 
10 grams; citric acid, 20 grams; distilled 
water, to 1000 c.c. (i liter). Fill the 
albuminometer tube with the urine to the 
letter U, then add the reagent to R, close 
the tube with the stopper, and invert several 
times, until the urine and the reagent are 
thoroughly mixed. Stand the tube in a 
rack for twenty-four hours, and then read 
off the number of grams of albumin to the liter, as will be 
indicated by the number on the side of the tube on a level 
where the albumin settles. If it is desired to know the 

^ Devoto, " Zeitschr. f. physiol. Ch.," XV, 474, 1891. 
2 Esbach's tubes are supplied by Eimer & Amend, of Third Avenue, New 
York, at a moderate cost. 




Fig. 16. — Esbach's 
albuminometer. 



134 ABNORMAL CONSTITUENTS OF URINE. 

percentage of albumin in the urine instead of the number 
of grams per hter, remove the decimal point one figure 
to the left ; thus, 5 grams per liter would be o. 5 per cent, 
of albumin. It will be observed that Esbach's albumin- 
ometer tubes are so graduated that their highest range is 
7 grams per liter — 0.7 per cent, of albumin. If, therefore, 
the urine be highly albuminous, it should be diluted with 
one or two volumes of water before testing, and the pro- 
duct multiplied by two or three, according as the volume 
is doubled or trebled. 

Centrifugal Method — Potassium Ferrocyanide and 
Acetic Acid. — Albumin can be readily precipitated by 
means of a mixture of potassium ferrocyanide and acetic 
acid, and quantitated by using the graduated tubes of a 
centrifugal apparatus. 

Process. — Take 10 c.c. of filtered urine, add 3.5 c.c. of a 
solution of potassium ferrocyanide (i : 10), and 1.5 c.c. 
of acetic acid (U. S. P.) ; close the tube with the thumb, 
and invert several times in order to mix thoroughly. The 
tubes are then placed in the centrifuge, w^hich is revolved 
until the precipitate of albumin has been completely set- 
tled and the supernatant fluid is perfectly clear. The cen- 
trifuge should be run at the speed of 1000 revolutions per 
minute and for from three to five minutes. According to 
Purdy, each -^ c.c. of precipitate represents i percent, bulk 
measure, or volume per cent, of albumin. 

In order to determine the percentage of albumin by 
weight in the use of the above method the writer, a few 
years ago, made a series of experiments which led to the 
following conclusion : each -^ c.c. of precipitate represents 
-^ of I per cerit. of albumiu by weight. 

An important source of error in this test is a separation 
of amorphous urates that may occur when the reagent, es- 
pecially the acetic acid, is added to a concentrated urine or 
one containing a relatively large amount of urates in solu- 
tion ; also when a deposit of urates is present previous to 
the addition of the reagent. When this exigency exists, 
centrifugalize the precipitate consisting of albumin and 
urates, decant the clear supernatant fluid, add hot water, 
which dissolves the urates, and centrifugalize again. The 
remaining deposit represents the amount of albumin present. 

This method furnishes a very rapid, accurate, and conve- 
nient means of quantitating albumin. The most important 
part of the test is to t/ioroughy settle the precipitate. 



GLOBULIN. 135 



GLOBULIN. 

Serum globulin, also termed paraglobulin, is a proteid 
which is usually associated with serum albumin, and is fre- 
quently found in the urine. Globulin is insoluble in water 
and soluble in dilute (i per cent.) solutions of sodium chlo- 
ride. It is also soluble in dilute acids or alkalies, being 
changed into acid- and alkali-proteid respectively, unless 
the acids and alkalies are exceedingly dilute and their action 
is not prolonged. It is precipitated by saturating its solu- 
tions with magnesium sulphate, with sodium chloride, and 
by half-saturation with ammonium sulphate. Globulin can 
be quantitated by saturating its neutral solution with magne- 
sium sulphate, since the other proteids are not precipitated 
by it. It is partially precipitated from its solution by 
carbonic acid gas. When its solutions are dialyzed, it is 
precipitated, owing to the fact that the percentage of salt is 
so far reduced by dilution that it is no longer sufficient to 
hold the globulin in solution. Its dilute saline solutions 
coagulate on heating to 75° C. (Halliburton). 

Normal urine is free from globulin, but this proteid may 
be found in the urine under pathologic conditions. 

Clinical Significance. — The clinical significance of the 
presence of globulin is much the same as that of albumin. 
It has been found in abundance in amyloid infiltration of 
the kidneys (in much larger quantities than in other forms 
of Bright's disease — Senator), acute nephritis, chronic cys- 
titis, pyonephrosis,^ following deranged digestion, and in 
the severe hyperemia following cantharides poisoning. 
Although globulin is usually present in the urine in much 
smaller quantities than albumin, it may equal or even exceed 
it in amount. It is occasionally found in the urine when 
albumin is absent. In severe organic disease of the kidneys 
and in the albuminuria that occurs in diabetes, Maguire ^ 
found that the proportion of albumin to globulin was as 
2.5 :i (normal in the Mood, 1.5 : i). 

Detection. — Saturate the urine, which has been pre- 
viously neutralized and filtered, with magnesium sulphate ; 
a white precipitate results if globulin is present. 

When a few drops of the globulin-containing urine are 
allowed to fall into a large volume of distilled water, a tur- 

^ " Boston Medical and Surgical Journal," March 3, 1898, p. 197. 
2 "British Medical Journal," vol. ii, 1886, p. 543. 



136 ABNORMAL CONSTITUENTS OF URINE. 

bidity appears (nucleo-albumin gives a similar turbidity) ; 
when much globuUn is present, the water assumes a milky 
opalescence. 

Quantitative Estimation of Globulin. — Take loo cc. 
of the urine-containing globulin, render neutral or faintly 
alkaline with amnionic hydrate, and remove the precipitated 
phosphates by filtration ; then completely saturate with 
magnesium sulphate ; filter, and wash with a saturated solu- 
tion of magnesium sulphate. The entire precipitate on the 
filter-paper is then dissolved in water or a weak solution 
of sodium chloride, and the globulin coagulated by boil- 
ing, the solution having been previously faintly acidu- 
lated with acetic acid. The coagulation must be com- 
plete. Filter through a previously dried and weighed 
filter-paper. The filter containing the precipitate is then 
dried at a temperature of iio° to 120° C, cooled, and 
weighed. The difference between the filter-paper and 
filter-paper plus precipitate equals the quantity of globulin 
in 100 cc. of urine. 

This test is probably not perfectly accurate, since small 
amounts of other proteids, notably some forms of albumose,^ 
are precipitated by magnesium sulphate. 

ALBUMOSES. 

This proteid belongs to the general class of proteoses. 
The albumoses, together with another proteose, — globidose, 
— are absent from normal urine (except perhaps in the 
slightest traces), but are occasionally found under patho- 
logic conditions. Up to the present time very little, if any- 
thing, is known of the clinical significance of the globu- 
loses, so that they will not be considered here. 

The albumoses are formed by the action of the gastric 
and pancreatic juices on proteid material, and appear as 
intermediate products between the proteid material and the 
final product, peptone. 

Varieties. — According to Kiihne, there are at least two 
albumoses — antialbiunose^ the forerunner of antipeptoiie, and 
hemialbitinose, the forerunner of jLemipeptone. Of these two 
forms hemialbiLinose is the more important. Kiihne and 
Chittenden, in their earlier work,^ at first distinguished 

1 Halliburton, "Text-book of Chem., Physiol., and Pathol.," p. 783. 

2 "Zeitschr. f. Biol.," Bd. xix, 1883, S. 174. 



ALBUMOSES. 137 

between a soluble and insoluble form, but more recently 
thev have described four closely allied, though dis- 
tinct forms of albumose.i (i) Protalhimose, soluble in 
hot and cold water and precipitated by saturation with 
sodium chloride and magnesium sulphate. (2) Hetero- 
albiimosc, insoluble in hot and cold water, soluble in dilute 
{0.5 per cent) and in more concentrated (15 per cent) 
solutions of sodium chloride, but precipitated from these by 
saturation with the salt. It is precipitated by alcohol, 
when it is partly converted into (3) dysalbumose, which is 
insoluble in saline solutions. (4) Dciitei'o-albuniose soluble 
in hot and cold water, not precipitated by saturating with 
sodium chloride or magnesium sulphate, unless an acid be 
added at the same time, but is precipitated by saturating 
with ammonium sulphate and by nitric acid, if an excess is 
not added. 

Clinical Significance. — Albumose was first discovered 
in the urine by Bence Jones ^ in a case of osteomalacia. 
It has since been found in this disease by Kiihne ^ and 
others. Virchow ^ has found albumose in the bone-marrow 
in cases of osteomalacia ; Hoppe-Seyler ^ found it in several 
cases of atrophy of the kidneys ; Lassar ^ found it in the 
urine of people who had been rubbed with petroleum, and 
Oertel "^ in a few cases after severe exertion. Senator has 
found albumose in the urine in croupous pneumonia, diph- 
theria, tertiary syphilis, carcinoma, hemiplegia, and muscu- 
lar atrophy. It has been found by a number of observers 
in sarcomata of the bones of the trunk, especially of the 
ribs and sternum. Fitz ^ has reported a case of myxedema 
in which albumosuria was a prominent feature. 

H. Senator ^ has recently reported a case of multiple 
sarcomatosis of the ribs in which albumosuria was a promi- 
nent feature. His patient also suffered from chronic paren- 
chymatous nephritis with amyloid infiltration of the kidneys, 

1 "Zeitschr. f. Biol.," Bd. xx, S. 11. 

2 «'Phil. Trans. Roy. Soc," vol. I, 1848. 

3 "Zeitschr. f. Biol.," xix, S 209. 
*" Virchow' s Archiv," iv, S. 309. 

5 "Physiol. Chem.," S. 858. 

6 " Virchow's Archiv," LXXVII, S. 164. 

■^ " Ziemssen's Handbuch d. Therapie," 1884. 
^ " American Jour. Med. Sciences," July, 1898. 
^"Berliner klin. Wochenschr.," Feb. 20, 1899. 



138 ABNORMAL COXSTITUEXTS OF URINE. 

fibrinous pleuris}', bronchopneumonia, and gangrene in the 
region of the left trochanter. 

The quantity of albumose found in the urine of croupous 
pneumonia, diphtheria, tertiary syphiHs, carcinoma, muscu- 
lar atrophy, after severe exertion, etc., is usually very small, 
it being present only in traces ; in cases of sarcomata of 
the bones of the trunk the quantit}' ma}' reach as high as 
^2 of I per cent. 

Although the condition of albumosuria has been 
thoroughly studied by a number of able chemists and clin- 
icians, its true clinical significance, up to the present time, 
is very indefinite. The fact that albumose has been so fre- 
quently found in bone diseases would suggest a possible 
cause of the condition. 

Detection. — From a clinical point of view it is not essen- 
tial to distinguish between the various forms of albumose ; 
the following reactions suffice for its detection : 

1. Take a small portion of the urine in a test-tube, and 
waiin gently. A precipitate appears w^hich is redissolved 
on boiling and reappears on cooling. 

2. Acidulate the urine with acetic acid, and add a few 
drops of a saturated solution of sodium chloride. A pre- 
cipitate is formed which disappears on heating and reap- 
pears on cooling. 

3. Add a few drops of nitric acid to the urine in a test- 
tube. If the acid is not in excess, a precipitate is formed 
which disappears on boiling and reappears on cooling. 

4. Add acetic acid, avoiding an excess, and then a {^.w 
drops of a solution of potassium ferrocyanide (i to 10). A 
precipitate is formed which disappears on boiling and reap- 
pears on cooling. 

5. Completely saturate the urine (preferably, according 
to Kiihne, at boiling temperature) with neutral ammonium 
sulphate. Filter and wash the precipitate with a saturated 
solution of ammonium sulphate. Dissolve the precipitate 
in water or dilute sodium chloride solution, and, if albumose 
be present, its solution will give the biuret reaction. This 
method separates the albumoses from the peptones, the 
former being precipitated, the latter remaining in solution 
and appearing in the filtrate from the ammonium sulphate 
precipitate. 



PEPTONE. 139 



PEPTONE, 

Peptones are rarely, if ever, met with in the urine. They 
are the final products of gastric and pancreatic digestion of 
albuminous bodies, in so far as these final products are 
still true albuminous substances. When, however, the 
digestion (hydration) is continued, the peptones split up 
into simpler bodies, which are no longer proteid in charac- 
ter. Peptones are, furthermore, products of pathologic 
changes in the blood-corpuscles. They may also be pro- 
duced from albumin by the continued action of acids and 
alkalies, and it is said, also, by the decomposing action of 
bacteria, as well as the long-continued operation of a tem- 
perature of 130° to 143° C. 

Peptones are not coagulated by heat. They are not 
precipitated by nitric acid, ammonium sulphate, potassium 
ferrocyanide and acetic acid, but are thrown down by a 
mixture of picric and citric acids, tannic acid, phospho- 
molybdic acid, phosphotungstic acid, potassio-mercuric 
iodide (Tanret's reagent), mercuric chloride, and Millon's 
reagent. They are precipitated, but not coagulated, by 
alcohol. Peptone is very soluble in water, and is readily 
diffused through animal membranes ; albumoses are only 
slightly diffusible. 

Peptones exist in two forms : (i) Hemipeptone^ which is 
obtained by the action of trypsin on hemialbumose. When 
purified and digested with trypsin it yields much leucin and 
tyrosin, and in this respect alone does it differ from anti- 
peptone. (2) Antipeptone is formed as the result of 
digestion of antialbumose, but is not capable of yielding 
leucin and tyrosin when purified and subjected to the most 
prolonged action of the pancreatic juice. It, moreover, 
does not yield leucin and tyrosin when treated with 
sulphuric acid, and does not react with Millon's reagent. 
Peptone is not present in healthy blood or normal urine. 

Clinical Significance. — Peptone was first described in 
the urine by Gerhardt. ^ Up to the publication of the very 
able researches of Kiihne and Chittenden, most of the 
proteids classed as peptones were probably albumoses, or 
mixtures of albumoses and peptones, so that the early data 
concerning peptonuria are far from reliable. The proteid 

1 *'Deutsch. Archiv f. klin. Med.," v, 215. 



140 ABNORMAL CONSTITUENTS OF URINE. 

most liable to be mistaken for peptone is deutero-albumose, 
and it is highly probable that what has heretofore been de- 
scribed as urine-peptone has been chiefly, if not entirely, 
deutero-albumose. The author has thus far failed to meet 
with an instance of true peptonuria. 

A number of observers have described peptonuria in a 
variety of pathologic conditions : Suppurative diseases, em- 
pyema, croupous pneumonia, gangrene of the lung, small- 
pox, erysipelas, scarlet fever, typhoid fever, tuberculosis, 
acute rheumatism, cancer of the gastro-intestinal tract and 
liver, cerebral hemorrhage, phosphorus-poisoning, typhus, 
etc. Naturally, the accuracy of observation in connection 
with some of the above-mentioned diseases is doubted, 
since, previous to the work of Kijhne and Chittenden, 
nothing was known of the means of distinguishing between 
peptone and the albumoses. 

Detection. — The accurate detection of peptone depends 
upon its separation from albumose, and this is accomphshed 
as follows : The urine, first faintly acidulated with acetic 
acid, is completely saturated with ammonium sulphate, and 
filtered. The precipitate may consist of albumin, globulin, 
or albumose. The only proteid in the filtrate, however, is 
peptone, which can be detected by the biuret reaction, or 
by precipitation with tannic acid, potassio-mercuric iodide, 
picric acid, phosphotungstic acid, or phosphomolybdic acid. 
According to Kiihne, in order to separate completely the 
albumoses from the peptones the saturation with ammonium 
sulphate should be conducted at the boiling temperature. 
Furthermore, a single saturation with ammonium sulphate 
should not be depended upon for the removal of all of the 
albumose, but saturation should be repeated until precipita- 
tion fails to occur. 

Separation. — Chittenden recommends the following pro- 
cess for the separation of the peptone from the ammonium 
sulphate saturated solution. The fluid is concentrated 
somewhat, and set aside in a cool place for the crystalliza- 
tion of a portion of the ammonium salt. The fluid is then 
mixed with about one-fifth of its volume of alcohol, and 
allowed to stand for some time, when it separates into two 
layers, an upper one rich in alcohol, and a lower one rich 
in salts. The latter is again treated with alcohol, by which 
another separation of the same order is accomplished. The 
lighter alcoholic layers containing the peptone are united 



PEPTONE. 141 

and exposed to a low temperature until considerable of the 
contained salt crystallizes out. The fluid is then concen- 
trated, and after the addition of a little water is boiled with 
barium carbonate until the fluid is entirely free from ammo- 
nium sulphate. Any excess of baryta in the filtrate is 
removed by the cautious addition of sulphuric acid, after 
which the concentrated fluid, reduced almost to a syrupy 
mass, is poured into absolute alcohol for the precipitation 
of the peptone. 

Biuret Reaction. — Take a small portion of the fluid to be 
tested in a test-tube, add an excess of sodic hydrate, and then add, 
drop by drop, a dilute solution of copper sulphate. The charac- 
teristic reaction is the appearance of a rose-red color. Great care 
must be exercised in the addition of the copper solution, since an 
excess of it gives a reddish-violet color, which is often misleading. 

The substances in the urine which give the characteristic 
biuret reaction are albumoses, peptones , and urobilin. Since 
more or less urobilin is present in every urine, it must be 
thoroughly removed before this test can be satisfactorily applied 
for the detection of albumoses and peptone. 



METHOD OF SEPARATION AND IDENTIHCATION OF 
PROTEIDS. 

The following table, proposed by Halliburton,^ gives the 
method for separating serum albumin, serum globulin, 
albumoses, and peptone, should they happen to be present 
together in the urine. This is a very rare occurrence, but 
in doubtful cases it is best to test for every one in the list : 

1. If the urine gives no precipitate on boiling after 
faintly acidulating with acetic acid, albumin and globulin 
are absent. If a precipitate occurs, albumin or globulin or 
both are present. 

2. If the urine after neutralization gives no precipitate on 
saturation with magnesium sulphate, globulin and hetero- 
proteose are absent. If such a precipitate occurs, one or 
the other is present. 

3. If the urine be saturated with ammonium sulphate 
and filtered, and the filtrate gives no xanthoproteic or biuret 
reaction, peptone is absent. 

4. If the urine gives no precipitate on boiling after acidu- 
lation, no precipitate with nitric acid, and no precipitate on 

1 *' Text-book of Chem., Physiology, and Pathology," p. 788. 



142 



ABNORMAL CONSTITUENTS OF URINE. 



adding ammonium sulphate to saturation, peptone can be 
the only proteid present. Confirm this by the biuret reac- 
tion. 

5. If all proteids are present, they may be separated as 
follows : 

Saturate the urine (faintly acidified with acetic acid) with 
ammonium sulphate. A precipitate is produced. Filter, 



{b) Filtrate. 
Contains peptone. 



[a) Precipitate. 

Contains albumin, globulin, het- 
ero- and deuteroproteose. Collect 
the precipitate on a filter, wash it with saturated solution of ammonium sul- 
phate, and redissolve it by adding a small quantity of water. To this solution 
add ten times its volume of alcohol ; a precipitate is formed ; collect this, and 
let it stand in absolute alcohol for from seven to fourteen days. Then filter 
off the alcohol, dry the precipitate at 40° C, extract it with water, and filter. 
An insoluble residue is left. 



(c?) Residue. 

This consists of albumin and glob- 
ulin coagulated by the alcohol. 



[b] Extract. 
This contains the proteoses in solu- 



Heterocaseose is precipitated by heating the solution to 65° C, or by satu- 
rating a portion of the extract with magnesium sulphate. Deuteroproteose 
remains in solution. 

Take another portion of urine, neutralize it, and saturate with magnesium 
sulphate. A precipitate is produced. Filter. 



(a) Precipitate. 

This consists of globulin and het- 
eroproteose, which may be separated 
by the prolonged use of alcohol, as 
above. 



[b) Filtrate. 

This contains albumin, deutero- 
proteose, and peptone. Add alcohol 
as above ; albumin is rendered insolu- 
ble in water in from seven to ten days. 
The deuteroproteose and peptone are 
soluble, and may then be separated 
by ammonium sulphate. 



NUCLEO-ALBUMIN (MUCIN?) 

A true nucleo-proteid, or nucleo-albumin is a combination 
of a nuclein with more albuminous matter.^ This form of 
proteid formerly known as mucin is probably not true 
mucin. The presence of small quantities of nucleo-albumin 
in the urine occurs under normal conditions, it being a pro- 
duct of the secretion of the cells lining the urinary tract. 
This substance is probably identical with the nucleo-albu- 
min of bile. 



1 A nuclein is a combination of some form of proteid matter with a nucleic 
acid (Chittenden). 



NUCLEO-ALBUMIN. 143 

Native nucleo-albumins contain approximately 1.5 per 
cent, of phosphorus, are, amorphous, and insoluble in water, 
but they dissolve in weak solutions of the neutral salts. 
They are completely precipitated by saturating their solu- 
tions with ammonium sulphate, and only incompletely pre- 
cipitated when their solutions are saturated with magnesium 
sulphate, or sodium chloride. They are soluble in alkaline 
hydrates and carbonates, and are readily precipitated from 
these alkaline solutions by means of strong mineral acids. 
They are, however, soluble in acetic acid and dilute mineral 
acids, and in this respect they differ from the nucleins. 

When nucleo-albumin is dissolved in a solution of so- 
dium chloride and boiled, a precipitate separates. It is 
precipitated by all of the reagents used for the precipita- 
tion of albuminous bodies, and gives all of the color reac- 
tions of proteid substances. When nucleo-albumin is 
repeatedly dissolved and precipitated, it becomes decom- 
posed, with the separation of a portion, which is rich in 
phosphorus. When it is subjected to the action of pepsin- 
hydrochloric acid, it furnishes a proteid and insoluble nu- 
clein. When some of the nucleo-albumins are boiled with 
moderately dilute mineral acids, a substance is produced 
which reduces an alkaline solution of cupric oxide with a 
resulting brown color; this reaction is considered by Morner ^ 
and Hammarsten ^ to be characteristic only of mucin. 

Clinical Significance. — Nucleo-albumin has been repeat- 
edly found in increased proportion in the urine of women, 
in which case it is derived chiefly from the genital tract. It 
is also found in increased amounts in urine that has passed 
over the irritated mucous membrane of some portion of the 
urinary tract. Such a urine is usually turbid when passed, 
and in a short time deposits a bulky cloud, usually found 
to contain a small, and sometimes a large, number of 
leucocytes, red blood-globules, and epithelial cells. It was 
first found in large quantities by Miiller in the urine of 
leukernia, and afterward by Malfutti and others in diphtheria, 
scarlatinal nephritis, cystitis, and after the use of pyrogallic 
acid, naphthol, and corrosive sublimate. It was also 
observed by Obermayer in the urine of a case of acute 
atrophy of the liver. Ott found it in abnormal quantities 
in the urine during high fever. Nucleo-albumin is always 
present in increased quantities in urine that contains bile. 

' K. A. H. Morner, ''■Skandin. Arch.," vi, 1895. 
2 Hammarsten, "Physiol. Chemie," 1895, 487. 



144 ABNORMAL CONSTITUENTS OF URINE. 

Detection. — For the detection of nucleo-albumin the 
urine is treated with an excess of acetic acid, when it is 
rendered turbid if much of this proteid be present. In 
testing a concentrated urine for nucleo-albumin it is advis- 
able to dilute it before acidulating, on account of the high 
proportion of salts, which retain nucleo-albumin in solution 
even in the presence of an excess of acetic acid. In testing 
for the presence of nucleo-albumin in an albuminous urine 
it is necessary first to remove, by boiling, the great bulk 
of the serum albumin, and any serum globulin present. 
The fluid is then filtered, and allowed to cool before testing 
with acetic acid. 

Ott's method for the detection of nucleo-albumin is 
very serviceable : To the urine add an equal quantity of 
saturated salt solution (NaCl), and then Almen's tannin 
solution 1 is slowly added. If nucleo-albumin be present, 
even in small amounts, an abundant precipitate will fall. 

Von Jaksch recommends for the precipitation of nucleo- 
albumin a solution of acetate of lead. 

HEMOGLOBIN. 

Hemoglobin is the pigment of the red blood-corpuscles. 
It gives the reactions of a proteid, but differs from proteids 
in containing iron and in being crystallizable. It belongs 
to the group of compound proteids, and yields as cleavage 
products, besides very small amounts of volatile fatty acids 
and other bodies, c\i\Q.?iY proteid (96 per cent.) and a color- 
ing-matter, Jieinodii'oinogen (4 per cent.) containing iron, 
which in the presence of oxygen is readily oxidized into 
hematin (Hammarsten). 

Hemoglobin is found in two forms — /. e. (a), oxyheino- 
globui, that charged with oxygen and found in arterial 
blood, and presenting, in dilute solutions, two absorption 
bands between Frauenhofer's lines D and E ; and (li), reduced 
Jicnioglobin, that deprived of its oxygen and found in venous 
blood, and presenting a single absorption band between 
D and E, occupying a space about midway between the two 
bands of oxyhemoglobin. 

For further details concerning this subject see page 232. 

'^Almen's tannin solution consists of; Tannin, 5 grams; 25 per cent, 
acetic acid, loc.c. ; 40 to 50 per cent, methylated spirit, 250 c.c. 



FIBRIN. 145 



FIBRIN. 



Fibrin is the albuminous body that separates on the 
so-called spontaneous coagulation of blood, lymph, and 
transudations, as also on the coagulation of a fibrin- 
ogen solution after the addition of blood-serum or the 
fibrin ferment. It is an elastic, white, stringy substance, 
which is insoluble in water, ether, and alcohol. It is sol- 
uble with difficulty in solutions of sodium chloride (5 to 15 
per cent.), in solutions of potassium nitrate (6 per cent.), 
and in solutions of magnesium sulphate (5 to 10 per cent.). 
The substance that goes into solution when fibrin is dis- 
solved in saline solutions is undoubtedly a proteid of the 
globulin class. It is coagulated by heat, precipitated from 
its solutions by saturating them with magnesium sulphate, 
and also by dialyzing away the salt from such solutions. 
The temperature of coagulation is 60° to 75° C. in a 
sodium chloride solution, and 73° to 75° C. in a magnesium 
sulphate solution. Weak hydrochloric acid (0.2 per cent.) 
causes fibrin to swell up into a transparent jelly. Fibrin is 
slowly dissolved by the strong acids, with the formation of 
acid albumin or syntonin, and albumoses. Fibrin is readily 
digested by pepsin in the presence of hydrochloric acid 
(0.2 per cent.), and by the pancreatic juice, with the result- 
ing formation of albumoses and peptone. Fibrinogen, 
which has also been found to have the properties character- 
istic of globulin, is the fibrin-precursor in blood plasma. 

Clinical Significance. — Fibrin most commonly appears 
in the urine as an accompaniment of blood, whether the 
blood comes from the kidneys or some other part of the 
urinary tract. Usually, if there is an extensive hemorrhage 
into the urinary tract, fibrin is abundant, and, on the other 
hand, if only little blood is present, the quantity of fibrin is 
small. But fibrin may be present in the urine when blood- 
corpuscles are absent ; thus, the so-called coagidablc urine, 
which, - upon standing some time, forms the fibrinous 
coagula. The extent of coagulation depends upon the 
quantity of fibrin present ; sometimes only a sticky sedi- 
ment forms in the bottom of the sediment-glass ; more 
rarely, the urine is converted into a gelatinous mass. 

Detection. — Fibrin is insoluble in water ; it is also insol- 
uble in sodic hydrate, in which respect it differs from albu- 
minous substances. If washed, fibrin is dissolved in a solu- 



146 ABNORMAL CONSTITUENTS OF URINE. 

tion of sodic carbonate (one per cent.) with the aid of gentle 
heat, and its solution gives the xanthoproteic and Millon's 
reaction for proteids. It is readily digested by artificial 
gastric juice. 

Fibrin should not be mistaken for the grayish, ropy mass 
that usually forms in purulent, alkaline urines, alkaline 
from the ammonia and ammonium carbonate resulting from 
the decomposition of the urea. (See p. 239.) 



CHAPTER V. 



CARBOHYDRATES- 

The carbohydrates, which are either normally or abnor- 
mally present in urine, resemble one another in a few of 
their chemic characteristics. All are hydrocarbons con- 
taining five or six atoms of C, or a multiple thereof; ex- 
cepting inosite, all have a strong rotary power over polar- 
ized light, are soluble in water, and have a neutral reaction. 

Normal urine under physiologic conditions contains a 
small amount of carbohydrates, among which are animal 
gum and also grape-sugar, but in amounts which can not 
be recognized by the ordinary sugar reactions. The glu- 
coside — mucin — increases the proportion of carbohydrates 
in the urine. 

Glucose, pentose, lactose, levulose, cane sugar, inosite, gly- 
cogen, and the like are not infrequently found abnormally 
in amounts sufficient to respond to certain chemic tests, and 
under such circumstances they are of pathologic interest. 
The most important of these, from a clinical point of view, 
is glucose. 

GLUCOSE. 

CoHioOfi. 

(Diabetic Sugar, Dextrose, Grape-sugar.) 

Careful chemic examinations have shown it to be highly 
probable that normal urine contains traces of sugar. ^ 
Under pathologic conditions glucose is present either 
temporarily — glycosuria — or permanently — diabetes mel- 
litus. (See Diabetes Mellitus, p. 370.) 

Glucose crystallizes in colorless, transparent prisms, 
which collect in bundles or in hard, tenacious crusts. It is 
soluble in its own weight of water, slightly soluble in cold 

1 Neubauer and Vogel, *' Analyse des Harns," Bd. i, 1898, S. 62. 
147 



148 ABNORMAL CONSTITUENTS -OF URINE. 

alcohol, more readily in hot alcohol, and insoluble in ether. 
Animal charcoal extracts it from its solutions (Bence Jones ^ 
and Seegen^). Solutions of glucose turn the rays of polar- 
ized light to the right (dextrose), and, according to the last 
accurate determinations of Tollens, ^ the specific rotation of 
the aqueous solution was found to be + 52.5°. In alka- 
line solutions it reduces the salts of copper, bismuth, 
mercury, and silver ; in the copper tests the cupric oxide 
is reduced to cuprous oxide (suboxide of copper). Glu- 
cose forms an osazone with phenylhydrazin, — phenylgluco- 
sazone (Plate 4), which crystallizes in highly characteristic 
groups of yellow needles. 

Isolation. — Grape-sugar may be separated from the 
urine in a number of ways, but the most practical method 
is that advised by Salkowski.^ 

Salkowski' s Method. — Take 20 c.c. of urine and add 
10 c.c. of a 1.6 normal solution of copper sulphate (with 
199.52 grams of copper sulphate to the liter), and 17.6 c.c. 
of normal sodic hydrate. After twenty to thirty minutes, 
dilute with lOO c.c. water, and filter. When the fiuid has 
passed through, the filter-paper is immediately placed on 
bibulous paper and entirely freed from the rest of the fluid. 
The precipitate is then dissolved in 50 c.c. of dilute hydro- 
chloric acid (i of hydrochloric acid, specific gravity 1 120, to 
10 of water), the copper removed by sulphuretted hydro- 
gen, the filtrate exactly neutralized with sodic carbonate, 
and evaporated to 20 c.c. This fluid is then to be tested 
for sugar, either qualitatively or quantitatively. Salkowski 
claims that 0.5 per cent, of sugar can be detected in urine 
in this way. Einhorn has detected as little as 0.05 per cent, 
of sugar by this method. 

Detection of Sugar in Urine. — The copper tests, which 
depend upon the power that grape-sugar possesses in alka- 
line solution of reducing the oxide of copper to lower 
oxides, are perhaps more commonly used than all others 
for the detection of sugar in the urine. It is safe to say 
that they are the most convenient and rapid of all tests that 
are capable of being applied by the student and practitioner 
of medicine. 

1 "Lancet," I, i86i, No. 3. 

2 " Pfliiger's Archiv," v, 375, 1872. 

3 " Berichte der chem. Gesellsch.," xvii, 2234, 1884. 
■* " Zeitschr. f. physiol. Ch.," iii, 96, 1879. 



GLUCOSE. 149 

The oldest of the copper tests is Trommer's, in which 
the hydrate of copper is set free at the time of its apphca- 
tion by an excess of sodic or potassic hydrate. 

Trommer's Test. — i. Take a third of a test-tube of 
urine, render alkahne with sodic or potassic hydrate. To 
this mixture then add, drop by drop, a weak solution (five 
per cent.) of sulphate of copper, shaking the mixture after 
each addition, until a deep-blue solution is obtained, or until 
the cupric hydrate, which forms as the copper is added, fails 
to dissolve. The upper one-half of the mixture is then 
boiled, and if sugar be present, a yellow precipitate of sub- 
oxide of copper soon forms. 

2. A second similarly prepared mixture of these ingre- 
dients may be made and set aside for from six to twenty- 
four hours without the addition of heat. If sugar be 
present, a similar precipitate of cuprous oxide will take 
place. If the reaction, with heat, is at all doubtful, it is 
important that this control-test should be made, since, as 
Neubauer has pointed out, most of the organic substances 
that reduce copper do so only when heated or after pro- 
longed boiling. 

Fehling's Test. — This test is performed by the use of 
Fehling's solution, which is prepared according to the 
original fonmtla, as follows : Pure crystallized cupric sul- 
phate, 34.639 grams ; a solution of caustic soda, — specific 
gravity 11 20, — about 500 c.c. ; chemically pure crystallized 
neutral sodic tartrate, 173 grams. Prepare by dissolving 
the sulphate of copper in 100 c.c. of distilled water; next 
dissolve the neutral sodic tartrate in the solution of caustic 
soda, and add the copper solution, little by little ; finally, 
bring the whole volume to lOOO c.c. (i liter) with distilled 
water. Ten cubic centimeters of this solution require 50 
milligrams of sugar to completely reduce it. 

It is a well-known fact that Fehling's solution prepared 
in the manner described soon decomposes on standing, 
and therefore becomes unfit for use. Furthermore, it has 
been found (Soxhlet) that the solution as previously given is 
too concentrated to obtain a delicate reaction. TJie folloiv- 
ing modification of Fehling's solution is therefore recom- 
mended for the purpose of obtaining a permanent solution, 
and one which also furnishes a rapid and yet delicate reac- 
tion. The solution is divided into two parts — viz., copper 
solution (A) and alkaline tartrate solution (B). 



1-0 ABNORMAL CONSTITUENTS OF URINE. 

A. Cupric sulphate 34-639 grams. 

Distilled water ad looo c.c. 

B. Sodio-potassium tartrate ( Rochelle salt) . 173 grains. 
Sodic hydrate (specific gravity Ii20j^ . . 500 c.c. 
Distilled water ad 1000 *•' 

These solutions — A and B — are to be kept in separate 
bottles and in a dark place. Equal parts of the two solu- 
tions produce diluted Fehling's solution. It will be seen 
that the combined volume of the two solutions amounts to 
2000 c.c, or one-half the strength of the solution of the 
original formula. Therefore, 20 c.c. of the combined mix- 
ture (10 c.c. of each) require 50 milligrams of sugar to 
completely reduce it. 

Process. — Qualitative Test. — Take equal parts of the 
two solutions — A and B, about one fingerbreadth of 
each — in a test-tube, and boil. If the Fehling's solution 
remains clear on boiling, then add 20 to 30 drops of the 
suspected urine which is free from albumin. Do not boil 
after the addition of the 2Lrine. If much sugar be pres- 
ent, a yellow or red precipitate of suboxide of copper 
readily appears. In case the quantity of sugar in the urine is 
less than i per cent, the reduction will not appear until after 
several minutes — five to thirty. If a reduction does not 
take place in thirty minutes, it is advisable to let the test 
stand for from eighteen to twenty-four hours, since traces 
of sugar show evidence of a reduction of the copper only 
after several hours, when a small amount of the suboxide 
will be found in the bottom of the test-tube. Less time is 
required for the test if the urine is gently heated previous 
to its being added to the boiling Fehling's solution. The 
nonappearance of a suboxide precipitate shows that the 
urine is free from sugar. 

In the hands of the author Fehling's test, performed in 
the manner previously indicated, is one of the most delicate 
and reliable tests available for routine work. The phenylhy- 
drazin test is more delicate than Fehling's, but is less suit- 
able for routine examinations on account of the length of 
time required for the performance of the test. (See p. 

152.) 

If the two solutions, which constitute Fehling's solution, 
are kept in separate bottles and mixed at the time they are 

1 Sodic hydrate, having a specific gravity of 11 20, is prepared as follows: 
Caustic soda, 52.727 grams ; distilled water, sufficient to make 500 c.c. 



GLUCOSE. 151 

to be used, there need be no fear that the solutions will 
decompose, even after keeping them several months. 

Professor Haines, of Chicago, has advised a modification 
of Fehling's solution, ^ and claims that the solution prepared 
according to his formula is stable, and, although kept on 
hand indefinitely, it may always be depended upon to be 
in good order for testing. 

Haines' Test (Simplified Fonmdd). — Take pure copper 
sulphate, 30 grains ; distilled water, ^ of an ounce ; make a 
perfect solution, and add pure glycerin, ^ of an ounce ; 
mix thoroughly, and add 5 ounces of liquor potassae. In 
testing with this solution take about I dram and gently boil 
it in an ordinary test-tube. Next add 6 to 8 drops (not 
more) of the suspected urine, and again gently boil. If 
sugar be present, a copious yellow or yellowish-red precipi- 
tate separates ; if no such precipitate appears, sugar is absent. 

On account of the decomposition of Fehling's solution 
on standing, Schmiedeburg has suggested the substitution 
of 1 5 grams of pure mannite for the neutral sodic tartrate 
of Fehling's solution. The mannite should first be dis- 
solved in 100 c.c. of distilled water, then 500 grams of the 
solution of caustic soda, specific gravity 1 140, should be 
added, and the solution completed according to the original 
formula for Fehling's solution. 

With the same end in view 173 grams of pure glycerin 
have likewise been substituted for the neutral sodic tartrate 
of Fehling's solution. 

When the proper precautions are observed, reliable re- 
sults may be expected with Fehling's solution, with saccha- 
rine urine which contains about -j^ of i per cent, of sugar. 

Precmtdons and Errors. — These are applicable to all cop- 
per tests : 

I. If the urine contains more than a trace of albumin, it 
must be removed, as it interferes with the reduction of the 
oxide of copper. 

2.^ When the mixture of urine and reagent is allowed to 
stand several hours without boiling, a considerable quantity 
of sugar is necessary before a satisfactory reaction occurs. 

3. The mixed urine and reagent should never be heated 
or boiled, since, as already stated, there are often organic 
substances other than sugar in the urine, which have, in the 

^ Purdy, " Practical Urinalysis," p. 103. 



152 ABNORMAL CONSTITUENTS OF URINE. 

presence of heat, a reducing action on an alkaline solution 
of cupric oxide. These substances are uric acid, urates, 
kreatinin, hippuric acid, mucin, hypoxanthin, glycuronic 
acid, alkapton, alkaloids, arsenic, and carbolic acid. Uric 
acid is the chief source of error, and should always be 
borne in mind in the use of the copper tests. 

4. The flocculent precipitate of earthy phosphates that is 
thrown down by the alkaline hydrate should not be mis- 
taken for the suboxide of copper. Such a precipitate is 
either colorless or of a greenish hue. 

5. Decolorization of the reagent by the urine should not 
be mistaken for a reduction of the copper. There must be 
an actual yellow or red precipitate. Any highly acid 
normal or pathologic urine may have a decolorizing action 
on the copper reagent. 

6. Too strong a solution of copper should not be used, 
since, in the presence of heat, a yellow or greenish-yellow 
color is often produced. This color may not appear until 
the mixture has cooled. 

Phenylhydrazin Test. — The phenylhydrazin test for 
sugar is applied as follows : To 50 c.c. of the suspected 
urine add i or 2 grams of hydrochlorate of phenyl- 
hydrazin, 2 grams of sodium acetate, and heat on a 
water-bath for one hour ; or add 10 to 20 drops of pure 
phenylhydrazin and an equal number of drops of 50 per 
cent, acetic acid, and heat as before. On cooling, if not 
before, phenylglucosazone separates out as a crystalline or 
amorphous precipitate. If upon microscopic examination 
the precipitate is found to be amorphous, it is dissolved in 
hot alcohol, and the solution diluted with water, and boiled 
to expel the alcohol, whereupon the compound is obtained 
in the characteristic form of yellow needles. It is claimed 
that by this method it is possible to obtain the crystals from 
a urine that contains only o. i 5 gram of sugar per liter, or 
0.015 per cent. (Williamson). 

Williamson has modified the phenylhydrazin test for 
sugar, as described in the work on urinary analysis by 
Hoffmann and Ultzmann, and has found it very useful. 

Williamson's Test.^ — "A test-tube of ordinary size is 
filled for about half aji inch with hydrochlorate of phenyl- 
hydrazin (in powder) ; then acetate of soda in powder (or 

1 Williamson," Diabetes Mellitus and its Treatment," 1898, p. 25. 



GLUCOSE. 153 

small ctystals) is added for another Jialf-mch. The test- 
tube is then half filled with urine, and boiled over a spirit- 
lamp. In performing the test I have not attempted to dis- 
solve the salts by shaking the tube, but have simply applied 
the flame of the lamp to the bottom of the tube, and the 
powders have soon passed into solution. After the urine 
has reached the boiling-point I have always continued to 
boil for about tivo inimitcs. The tube is then left in the 
test-stand, and examined again some time afterward." 

If sugar be present, a yellowish deposit forms at the 
bottom of the tube, and on microscopic examination it is 
seen to consist chiefly of beautiful needle-shaped crystals 
of a bright sulphur-yellow color. If no sugar is present, 
only brownish amorphous globules or yellow scales are 
found in the deposit. By performing the test in this simple 
manner Williamson has never obtained any crystals of 
phenylglucosazone in normal urine. 

Much discussion has arisen concerning the proper method of 
performing this test for sugar. According to Hirschl, ^ if a mix- 
ture be left on a water-bath for a shorter time than one hour, a 
glycuronic acid compound (melting-point, 150° C.) is formed, 
which is liable to be mistaken for phenylglucosazone. On the 
other hand, it has been pointed out by a number of observers 
that if the mixture be kept on a water-bath for as long a period 
as one hour, a small deposit of the crystals may be obtained in 
many normal urines. These crystals are frequently of a doubt- 
ful nature, even after they have been dissolved in hot alcohol 
and recrystallized. 

According to Fischer, the reaction which takes place be- 
tween phenylhydrazin and glucose is represented by the 
following equation : 

CeH,Pg + 2CeH. . N2H3 = C,3H,,NA + 2H,0 + 2H. 

A great advantage of the phenylhydrazin test for sugar 
is that it gives no reaction with uric acid, kreatinin, hip- 
puric acid, pyrocatechin, etc., while with Fehling's test, as 
ordinarily applied (boiling the urine and Fehling's solution 
together), these substances are often a source of fallacy. 

Phciiylghicosazone (Q^fi^^ fi^ zr^^\.2XX\z^?, in bright, fine, 
yellow needles (see Plate 4), which are arranged singly 
or in stellate groups. They are almost insoluble in water, 

1 '* Zeitschr. f. physiol. Ch.," XIV, 377. 



154 ABNORMAL CONSTITUENTS OF URINE. 

but dissolve in boiling alcohol, and melt at 204° to 
205° C. 

Fermentation Test. — The fermentation test is an excel- 
lent and reliable one for the detection of sugar (glucose) in 
all cases in which the urine contains more than ^ of i 
per cent, of sugar. The test depends upon the fermenta- 
tion of the sugar by means of yeast, yielding alcohol, car- 
bon dioxide, and various other less important substances, 
with a resulting decrease in the specific gravity. The fol- 
lowing equation represents the reaction which takes place : 

C6H,A = 2C2HeO + 2C02. 

The most convenient method of applying this test is as 
follows : Take a test-tube, preferably one of large diameter, 
introduce into it a piece of compressed yeast about the 
size of a pea, and fill the test-tube to the top with the 
urine to be tested. Stopper tightly with a rubber cork 
having a single perforation, through which a glass tube is 
passed so that it reaches nearly to the bottom of the test- 
tube. Above the cork the glass tube is bent at right 
angles to the perpendicular of the test-tube, and some four 
inches from this bend the tube is again given a right- 
angled bend downward. A receptacle is then placed 
under the end of the glass tube. 

If sugar is present, evidences of fermentation will pre- 
sent themselves, generally within twelve hours, by the for- 
mation of carbon dioxide which rises to the surface of the 
urine, but, being held in by the cork, forces the urine out 
through the bent glass tube into the receptacle at the end 
of the tube. Sufficient carbonic acid gas is usually obtained 
from highly saccharine urines to force out all of the urine 
in the test-tube. The test should be subjected to a tem- 
perature of 80° to 90° F. 

This test can not be relied upon if less than i^ per cent, 
of sugar is present, since a small quantity of carbon dioxide 
is likely to be absorbed by the urine (water will absorb an 
equal volume of carbonic acid gas). 

In the performance of this test it should be borne in 
mind that some specimens of yeast spontaneously evolve 
gas, and it is, therefore, best to perform with each urine 
tested a control experiment with yeast mixed with water 
instead of urine, in order to judge of the amount of gas in 
the yeast itself. 



Plate 4 




Crystals of Phenylglucosazone (after vonJaksch' 



GLUCOSE. 155 

The chief disadvantage of the fermentation test is that it 
requires several hours for its completion, and it is therefore 
not practical for routine work. 

Bismuth Tests. — These tests depend upon the power 
that sugar (glucose) possesses of reducing the salts of 
bismuth, with a resulting black precipitate of metallic 
bismuth. 

(rt) Bottger's Test. — Take one-fourth of a test-tube of the 
suspected urine, add an equal volume of potassic hydrate 
(liquor potassse, U. S. P.), or a solution of sodic carbonate 
(i part of crystals to 3 parts of distilled water), mix, and 
add a small amount of subnitrate of bismuth. Shake, and 
boil the whole mixture, and if sugar be present, a black 
precipitate appears, which clings to the sides of the test- 
tube. A gray, instead of a black, precipitate is obtained li 
the quantity of sugar is small, in which case a smaller 
amount of bismuth should be used in making the test. 
According to Tyson, this gray precipitate, said to be char- 
acteristic of small quantities of glucose, sometimes presents 
itself when no sugar is present. 

The urine to be tested should be free from albumin and 
other substances containing sulphur, since traces of sulphur 
combine with the bismuth salts to form bismuth sulphide, 
which is likely to be mistaken for metallic bismuth. To 
obviate this difficulty, Briicke has suggested the following : 

{b) Brucke's Modification of Bottger' s Test. — Frohn's 
reagent ^ is recommended for the removal of the sulphur 
compounds in the following way : Pour into a test-tube a 
certain quantity of water, say 10 c.c, and fill another tube 
to the same level with the suspected urine. To the first 
add a drop of Frohn's reagent, which will cause a pre- 
cipitate. Then add, drop by drop, concentrated hydro- 
chloric acid until the precipitate is redissolved. In this 
way the approximate quantity to be added to the suspected 
urine is ascertained. Acidulate the urine in the other test- 
tube with the same quantity of hydrochloric acid ; treat it 
with the reagent until precipitation is complete, and filter. 
The filtrate, which should not be rendered turbid on the 
further addition of hydrochloric acid or the reagent, is 
thoroughly boiled with an excess of sodic or potassic 

^ Frohn's reagent : 1.5 grams of freshly precipitated bismuth subnitrate are 
mixed with 20 grams of water, and heated to boiling ; then 7 grams of potas- 
sium iodide and 20 drops of concentrated hydrochloric acid are added. 



:l56 abnormal constituents of urine. 

hydrate, as in Bottger's test. If a gray or black precipitate 
or color is formed, sugar is present. Briicke claims that 
this test will detect 0.4 per cent, of glucose in water. 

(c) Ny lander's Test. — Almen's fluid is used. It consists 
of 4 grams of Rochelle salt (sodio-potassic tartrate), dis- 
solved in 100 c.c. of a 10 per cent, solution of caustic soda. 
The fluid is warmed, and 2 grams of subnitrate of bismuth 
are added. One volume of this fluid is added to 10 volumes 
of urine, and the mixture heated. In a few minutes (three 
to five) it will become black if sugar be present. The reac- 
tion will indicate the presence of at least o. i per cent, of 
sugar. This test is not applicable to albuminous urines, and 
the reaction occurs in the presence of melanin or melanogen, 
or when the fluid is rich in reducing substances other than 
sugar. 

Methylene-blue Test. — Methylene-blue is decolorized 
by glucose in a warm alkaline solution. In performing 
the test the diabetic or suspected urine is diluted (i part to 
9 of water). Of this diluted urine 2 c.c. are mixed with 
6 c.c. of a I : 3000 solution of methylene-blue, and 2 c.c. 
of potassic hydrate are then added. The mixture is boiled 
for one or two minutes, when the blue color disappears if 
sugar be present. Care must be taken that the fluid is 
shaken as little as possible, since the blue color returns 
easily, owing to the action of the oxygen in the air. It is 
important to dilute the urine, as all tinelihited urine dis- 
charges the blue color ; but normal urine diluted I : 9 of 
water does not decolorize methylene-blue. 

Williamson has found that a distinct reaction is obtain- 
able by this method w^hen diabetic urine is diluted until the 
percentage of sugar is only O.07, but when further diluted, 
until it is 0.014, no reaction is obtained. Urines rich in 
urates give a doubtful reaction when diluted I : 9. Since 
urine often contains reducing substances other than sugar, 
Frohlich ^ recommends that it be treated first with 5 c.c. 
of a concentrated solution of lead acetate, and Avith 5 c.c. 
of a solution of basic acetate of lead ; then take an equal 
quantity of the filtrate and a concentrated solution of 
methylene-blue (i : 300), add potassic hydrate, and boil, as 
previously indicated. This test is not so satisfactory as the 
phenylhydrazin or the F'ehling test. 

1 "Centralbl. f. inn. Med.," 1898, No. 4. 



GLUCOSE. 157 

Numerous other tests have been suggested for the de- 
tection of sugar in urine. The following may be men- 
tioned : Diazobenzolsulphonic acid (Penzoldt), picric acid 
(Johnson), sodium or potassium hydrate and heat (Moore), 
acetate of lead and ammonia (Rubner), alpha-naphthol and 
thymol (Molisch), and indigo-carmine (Miilder). Most of 
the above-named tests are greatly inferior to those that 
have been described. 

Quantitative Determination of Sugar in Urine. — A 
quantitative determination of the sugar should be made in 
all cases in which it has been detected. It is only by a 
knowledge of the quantity of sugar present that a diag- 
nosis of the condition can be made, the severity of the dis- 
ease ascertained, and the results of treatment judged. The 
twenty-four-hour quantity of urine should be accurately 
kept, and while it is being collected, put in a cool place to 
prevent fermentation. The entire secretion for the twenty- 
four hours should then be thoroughly mixed and measured, 
and a sample of this taken for the determination. The 
urine obtained at a single micturition should not be used 
for the quantitative test, for the reason that there is consid- 
erable variation in the quantity of sugar eliminated : ac- 
cording to the time of day, and the length of time after a 
meal. 

The total quantity in grams should in every instance be 
calculated. A knowledge of the percentage of sugar alone 
is never sufficient, for the percentage in itself means little if 
the total quantity is not determined. In routine work the 
percentage is usually obtained, but only for the sake of 
convenience in figuring the total number of grams of sugar. 

Fehling's Test. — This is one of the most practical 
quantitative tests for sugar in urine, and is conducted by 
the titration method, using the modified Fehling's solution, 
the formula of which is given on page 150. 

The process depends upon the fact that the blue color 
disappears, and that the copper is completely precipitated 
from a definite quantity of Fehling's solution by a given 
amount of grape-sugar ; thus, every 20 c.c. of the modified 
Fehling's solution used require 50 milligrams of sugar to 
completely reduce it. 

Necessary Apparatus (Fig. 17). — A Florence flask of 
250 (z.c. capacity ; a common retort-stand with a burette- 
holder attachment, and with a piece of copper- or iron-wire 



158 



ABNORMAL CONSTITUENTS OF URINE. 



gauze that is large enough to cover one of the rings of 
the stand (a tripod, the top of which is covered with cop- 
per-wire gauze, may be conveniently used) ; a 25- or 50-c.c. 
burette, which is graduated to tenths of a cubic centimeter ; 
a lo-c.c. pipette ; a loo-c.c. glass-stoppered graduate ; and 
a Bunsen burner or a large spirit-lamp. 




Fig. 17. — Apparatus for the quantitative estimation of sugar : m. Meniscus. 



The analysis should be conducted as follows : First take 
the specific gravity of the urine to be tested, then test for 
albumin, — preferably by the nitric acid test, — and if more 
than a trace be present, remove it according to the directions 
given on page 131. 



GLUCOSE. 159 

If the specific gravity of the urine is more than 1030, dilute 
it I : 10 with distilled water (urine, I ; water, 9) ; \{ less than 
1030, dilute it I : 5 (urine, i ; water, 4). Mix thoroughly, 
and pour the diluted urine into the burette, filling it to the 
zero mark, care being taken to expel all air from below the 
stop-cock. Next take 10 c.c. of eacJi of the solutions A 
and B by means of the lo-c.c. pipette, and place in the 
250-c.c. flask. Add 60 c.c. of distilled water, making the 
entire volume amount to 80 c.c. Place the flask on the 
wire gauze, and boil the mixture. After the diluted Feh- 
ling's solution has boiled for a short time, — say for two or 
three minutes, — and it is found that the solution does not 
show evidences of reduction, the diluted urine is added, 
drop by drop, from the burette into the Fehling's solution, 
which is kept boiling. When, on removing the flame, after 
a series of observations, it is found that the meniscus has 
lost its blue color and has become colorless,^ the reaction 
is complete. 

The inejziscus (Fig. 17, m), which is seen as a clear line 
(blue at first and later colorless), is best detected by plac- 
ing the flask between the eye and the light. As the eye is 
raised and lowered, this clear line will be seen just beneath 
the surface of the fluid. 

The blue color having disappeared from the mixture, the 
number of cubic centimeters of diluted urine employed is 
read off Since it takes just 50 milligrams (0.050 gram) 
of sugar to completely reduce the cupric oxide in the 20 
c.c. of Fehling's solution used, the percentage of sugar in 
the urine may be readily calculated, and from the per cent., 
the number of grams of sugar eliminated in twenty-four 
hours. 

Example : If 15 c.c. of dUuted urine were necessary to 
complete the test, and the urine was originally diluted i : 
10, then 15 ~- 10^ 1.5 c.c. of tmdUtited urine. Since 1.5 
c.c. of undiluted urine reduced the copper, and 50 milli- 
grams of sugar accomplish the same end, then 1.5 c.c. of 
urine must contain 50 milligrams of sugar. The percent- 
age is obtained according to the following proportion : 

1.5 : 0.050 : : loo : x 
^^ZZZ percent. 

1 When the test solution is allowed to stand for a short time after the test has 
been completed, it again becomes blue, due to the reoxidation by the oxygen 
from the air. This should not be mistaken for an incomplete reduction. 



160 ABNORMAL CONSTITUENTS OF URINE. 

Suppose the total quantity of urine in twenty-four hours 

"Z 'Z'Z ^X^ 2000 

amounted to 2000 c.c, then '^^^ ^ 66.6 p;rams,^ the 

' 100 » ' 

quantity of sugar in twenty-four hours. 

Precautions : i. The urine should be added to the boil- 
ing Fehling's solution, drop by drop, in order to obtain a 
suboxide precipitate that will settle in a very short time. 
If a considerable quantity of the urine is added at a time^ 
the precipitate will not settle well, and the meniscus can 
not be distinctly seen. 

2. A yellow color to the meniscus or to the body of 
the solution, besides that produced by the suboxide pre- 
cipitate, indicates that too much of the saccharine urine 
has been added, and that the end reaction has passed. A 
new titration is then necessary. 

3. The Fehling's solution should be kept at the boiling 
temperature, except during the time required for observing 
the meniscus. As soon as the solution cools, reoxidization 
of the copper begins, and consequently the blue color 
reappears. 

Purdy's Method. — The following modification of Feh- 
ling's method is advised by Dr. Purdy, who claims that by 
the use of his solution various defects of Fehling's method 
are overcome : 

Take of pure cupric sulphate, 4.752 grams ; potassium 
hydroxide, 23.5 grams ; strong ammonia (U. S. P. — specific 
gravity 0.9) 350 c.c. ; glycerine (C.P.), 38 c.c. ; distilled 
water, to make looo c.c. 

Prepare by dissolving the cupric sulphate and glycerine 
in 200 c.c. of distilled water with the aid of gentle heat. 
In another 200 c.c. of distilled water dissolve the potassium 
hydrate, mix the two solutions, and, when cool, add the 
ammonia. Finally, with distilled water bring the volume 
of the whole to exactly 1000 c.c. Thirty-five cubic centi- 
meters of this solution are reduced, upon boiling, by 
exactly 2 centigrams (0.02 gram) of grape-sugar. 

Proceed by accurately measuring 35 c.c. of the solution 
into the flask, dilute with about two volumes of distilled 

^ Since this method of figuring is based on the supposition that i c.c. is 
equal to I gram, the same as distilled water, it can not rightly be applied to 
urine, I c.c. of which weighs more than I c.c. of distilled water ; therefore, the 
figures 66.6 represent only the approximate quantity of sugar. Accurate figures 
may be obtained by correcting for the difference between the specific gravity 
of the urine tested and that of distilled water. 



GLUCOSE. 161 

water, and bring the whole thoroughly to the boiling-point. 
Fill the burette to the zero mark with the urine to be tested, 
and slozoly discharge the urine into the boiling test solution, 
drop by drop, until the blue color begins to fade ; then, 
still more slowly, three to five seconds elapsing after each 
drop, until the blue color completely disappears and the 
test solution is left perfectly colorless and transparent. The 
number of cubic centimeters required to discharge the blue 
color in 35 c.c. of the test solution contains exactly 2 centi- 
grams (o.02 gram) of sugar. 

If 35 c.c. of the test solution are reduced by 2 c.c. of 
urine, then 2 : 0.02 : : lOO : x, and x ^= i per cent, of 
sugar; reduced by I c.c, 2 per cent; reduced by ^ of a 
cubic centimeter, 3 per cent. ; reduced by )^ of a cubic 
centimeter, 4 per cent. ; reduced by ^^ of a cubic centimeter, 
8 per cent. 

If absolute accuracy of results is desired, it is better to 
dilute the urine to be tested with 2 volumes of distilled 
water, and divide the product by 3 ; especially if the per- 
centage of sugar is high. 

The advantages claimed by Purdy for this test are (i) 
its perfect end-reaction ; (2) the stability of the solution ; 
(3) its rapidity of application, only requiring about five 
minutes, and (4) its accuracy. 

Fermentation Test. — The fermentation test for sugar 
can not be considered an accurate quantitative test, although 
it may be used with advantage for determining the approxi- 
mate quantity of sugar present. The method suggested by 
Roberts is as follows : Four ounces of the saccharine 
urine are placed in a twelve-ounce bottle, and a piece of 
compressed yeast is added. The bottle is then stoppered 
with a nicked cork to permit the escape of the carbonic acid 
gas, and set aside in a warm place to ferment. Beside it 
is placed a tightly corked four-ounce bottle filled with the 
same urine, but without any yeast. In from eighteen to 
twenty-four hours fermentation will have ceased. The fer- 
mented urine is then decanted into a urinometer-glass, and 
the specific gravity taken. The specific gravity of the un- 
fermented urine in the other bottle is taken at the same 
time, and the loss of density ascertained. Roberts has. 
shown that every degree in the specific gravity lost in 
fermentation corresponds approximately to one grain of 
sugar per fluidounce. Thus, if before fermentation the 



162 ABNORMAL CONSTITUENTS OF URINE. 

specific gravity was 1 040 and after fermentation it is 
1020, it will have contained 20 grains of sugar to the 
fluidounce of urine. The two portions of urine in the 
bottles should be subjected to exactly the same tempera- 
ture. 

The percentage of sugar may be roughly ascertained by 
multiplying the number of degrees lost in the specific grav- 
ity by the arbitrary coefficient 0.23. 

In the hands of the writer the fermentation test yields 
results which are in the neighborhood of one-half per cent, 
below those obtained by using Fehling's solution. A 
decided objection to this method is that it requires from 
eighteen to twenty-four hours for the completion of the 
analysis. 

Einhorn has devised a fermentation apparatus that 
gives only approximate results. Two specially con- 
structed and graduated tubes are used, one of which is 
filled with a mixture of the suspected urine and a small 
quantity of yeast, and the other with a mixture of normal 
urine and yeast, as a control. The tubes are then set aside 
at a temperature of from 30°-34° C. (86°-93° F.), and left 
until fermentation has ceased. The percentage of sugar is 
then read off from the column of carbon dioxide present. 
If the second tube also shows a small amount of gas, the 
figure corresponding to the amount is deducted from the 
reading in the first tube. 

By Polarization. — Glucose, or grape-sugar, rotates the 
plane of polarized light toward the right, and upon this 
fact a quantitative test for that substance is based. 
Although a quantitative determination of grape-sugar by 
this method is theoretically accurate, when applied to urine 
it is open to fallacy, since the urine is apt to contain other 
substances such as laevulose, ,5-oxybutyric acid, etc., which 
rotate the plane of polarized light in the opposite direction. 
As pointed out by v. Jaksch, Hoppe-Seyler, and others, it 
is advisable to apply the test both before and after fermen- 
tation, and the difference in the results will represent the 
quantity of grape-sugar in solution. 

A large variety of polariscopes have been constructed 
for this purpose, among the best of which are those of 
Soleil, Laurent, Lippich, Ultzmann, Misterlich, v. Fleischl, 
and Schmidt & Haensch. In recent years the use of the 
half-shadow polariscope has rendered this quantitative test 



GLUCOSE. 



163 



more reliable, on account of the accuracy with which the 
extent of rotation is determined. 

The polariscope manufactured by Schmidt & Haensch, 
of Berlin, is one of the best.i It is a half-shadow instru- 
ment, being so made that gas or petroleum light can be 
used instead of a sodium light. It determines direct per- 
centages of sugar, and is not only accurate, but its operation 
is quick and simple. 





slllH 



Fig. i8. — The Schmidt & Haensch polariscope. 



In the Schmidt & Haensch apparatus, as "represented in 
figure 1 8, is the ocular; S, the ivory scale with vernier; 
L, the ocular by means of which the scale is read ; K, the 
screw-head by which the quartz wedge is moved ; B, the 
glass tube for holding the suspected fluid ; and P, the 
receptacle for the glass tube. 

1 This instrument can be obtained of Messrs. Eimer & Amend, 205-211 
Third Avenue, New York city. 



164 ABNORMAL CONSTITUENTS OF URINE. 

The source of light is a well-constructed lamp, with a 
flat burner, for either gas or petroleum ; a special lamp can 
be constructed so as to use electric light. The lamp should 
be removed about 30 cm. from the apparatus, and so 
adjusted that the illuminating lens in the chimney of the 
lamp shall be exactly central to the optical axis of the 
apparatus. In looking through the instrument a clear 
circular field should be seen, with a sharp perpendicular 
line between the two halves of the field. If the field is not 
perfectly distinct, the ocular (0) should be drawn out until 
the perpendicular line and the circular outline of the field are 
sharply defined. This adjustment should be made without 
the glass tube — that is, the receptacle should be empty and 
its cover closed. 

The delicate scale (F), on which are found numbers cor- 
responding to the principal lines, is read through the 
ocular (Z). The zero point on the vernier (S) should be made 
to correspond exactly with that on the scale (/^) by means 
of the adjustment-screw (^). When the zero point on the 
vernier is opposite that on the scale, the two halves of 

the field of the apparatus 
should exactly correspond — 
that is, they should be equally 
lighted. (See ^, Fig. 19.) If, 
however, the two halves of 
Fig. 19. the field should not receive 

an equal amount of light, 
they should be made to correspond exactly by the use of the 
adjustment-screw (^). The vernier (S) is then moved to 
the side corresponding by means of a micrometer-screw, 
until its zero point is opposite that on the scale (F). 

Having adjusted the apparatus, the glass tube is then 
filled with the suspected urine, and placed in the receptacle. 
The two halves of the field, which are then found to 
receive an unequal amount of light, are made to correspond 
by means of the adjustment-screw {^K\ and the rotation to 
the right or to the left read on the scale. The result is the 
percentage of sugar in the fluid. Every interval on the 
scale corresponds to ^ per cent., and between these inter- 
vals are lines which are equivalent to -^-^ per cent. 

Example. — If the scale is moved toward the left, the 
number of scale intervals that have been passed is reckoned 
from the zero point on the vernier. Suppose that the 




GLUCOSE. 165 

number of scale-intervals passed is 7, and that the zero 
point of the vernier stands between 7 and 8 and at the 
mark corresponding to 0.3 per cent, then 

7 half per cent. = 3-5 + 0.3 = 3.8 per cent. 

A similar reading is made when the scale is moved 
toward the right. In order to read direct percentages of 
sugar on the scale the 200-mm. tube should always be 
used. If it should be necessary, on account of the turbidity 
of the urine, to use the 100- or 50-mm. tubes, the reading 
in every instance should be multiplied by either 2 (lOO-mm. 
tube) or 4 (50-mm. tube). 

Grape-sugar rotates the plane of polarized light toward 
the right ; albumin rotates tow^ard the left. Consequently, 
in a urine containing both albumin and sugar the degree 
of rotation to the right or to the left will depend upon the 
predominance of one or the other of these substances. 

Precautions. — The urine must be clear ; if it is turbid, it 
should be filtered as rapidly as possible through a plaited 
filter of soft filter-paper. If the urine is then so highly 
colored that when the long glass observation tube (200 
mm.) is used the line of separation between the two halves 
of the field can not be distinctly seen, the shorter glass 
observation tube (lOO or 50 mm.) should be used. If the 
field is still indistinct, the urine should be shaken in a flask 
with pure, dry, animal charcoal, or decolorized by add- 
ing to the urine one-tenth of its volume of basic acetate of 
lead, and then filtered. In the latter instance the results 
obtained by polarization must be multiplied by ^, on 
account of the dilution. 

The temperature of the urine must be from 15° to 20° C. 
If the urine is free from albumin, the percentage of sugar is 
obtained directly by the use of the 200-mm. tube, in the 
manner mentioned. If, on the other hand, the urine con- 
tains albumin, a second polarization is necessary after the 
removal of the albumin. The albumin is removed as fol- 
lows : Take 100 c.c. of the urine in an evaporating dish, 
and place on a water-bath. Add acetic acid, drop by drop, 
continuing the heat until a flocculent precipitate appears. 
Filter as quickly as possible, cool, and add sufficient dis- 
tilled water to the filtrate to make 100 c.c. The result of 
the second polarization will represent the exact percentage 
of suear. 



166 ABNORMAL CONSTITUENTS OF URINE. 

LACTOSE, 

(Milk-sugar.) 

Lactose, C^.^H.^fi^^, is not infrequently found in small 
amounts in the urine of women (the maximum being about 
one per cent.) near the end of gestation, but more especially 
in nursing women in whom the flow of milk has become 
impeded, as in cases of mastitis. Lactose is also frequently 
seen in the urine of women who have weaned their children. 
Its presence may continue for from three to four days, and 
even a week, particularly in those in whom the secretion 
of milk is copious. Whereas lactose, when present, is an 
abnormal constituent of the urine, its presence can not be 
considered of pathologic significance. Its chief importance 
lies in the fact that it should, in all cases, be distinguished 
from glucose. 

Lactose crystallizes in colorless, four-sided prisms, with 
acuminated ends, bounded by four angles. The specific 
rota.ry power of lactose is -f 52.5°, and is independent of 
the concentration in solutions that contain up to 56 per 
cent, at ordinary temperatures. It reduces the salts of 
copper upon boiling in alkaline solution, but more feebly 
than grape-sugar. It does not undergo alcoholic fermenta- 
tion with yeast ; is quite soluble in cold, and freely soluble 
in hot, water ; insoluble in alcohol and ether. It is pre- 
cipitated by acetate of lead and ammonia (Briicke). 

Isolation. — According to F. Hofmeister, the following 
process serves for the isolation of milk-sugar : Since evapo- 
ration of the urine is liable to decompose the lactose, it is 
directly precipitated by a solution of acetate of lead and 
ammonia, and the precipitate is washed. The filtrate and 
wash-water should again be precipitated with lead acetate 
and ammonia, and the process repeated until the filtrate 
shows no more rotation. The washed precipitate is then 
suspended in cold water, and decomposed with sulphureted 
hydrogen. The solution is freed from the greater part of 
the hydrochloric acid by shaking with silver oxide, and 
from the remainder of the HCl by neutralizing the filtrate. 
The solution is once more treated with H.,S, and the mix- 
ture evaporated after the addition of barium carbonate. Be- 
fore the residue becomes syrupy it should be treated with a 
sufficient amount of 90 per cent, alcohol to produce a 
flocculent, rapidly settling precipitate. The filtrate, placed 



LEVULOSE. 167 

in a desiccator, yields crystals of lactose, which should be 
washed with dilute alcohol, then recrystallized from water 
after decolorizing with animal charcoal, and finally freed 
from adhering substances by boiling with 60 to 70 per cent, 
alcohol. These crystals are then subjected to the tests 
for lactose, including that with Barfoed's reagent. 

Detection. — If the urine reduces Fehling's solution 
feebly, does not ferment with yeast, and rotates the polar- 
ized light strongly to the right, lactose is probably present,' 
especially if the urine is that of a pregnant or nursing 
woman. A confirmatory test may be made by using the 
phenylhydrazin test, which, in the presence of lactose, forms 
an osazone. Phenyl-lactosazone crystallizes in the form of 
yellow needles, which are usually aggregated in clusters, 
and melts at 200° C, with the evolution of gas. Lactose, 
unlike glucose, does not reduce Barfoed's reagent,^ but 
this test can not be applied to urine, since Barfoed's re- 
agent is reduced to a slight extent by normal urine. 

The certain detection of lactose is secured only by iso- 
lating it from the urine. 

LEVULOSE. 

(Fruit Sugar.) 

Levulose, C^H^fiQ, is only rarely found to be a con- 
stituent of the urine. When present, it is usually found 
associated with grape-sugar, and is rarely, if ever, found 
alone. In such instances it usually happens that consider- 
ably more sugar is found in diabetic urine by titration than 
by polarization, thus showing the presence of a substance 
that rotates to the left. The diminution in the optical 
activity of the urine is not necessarily caused by a sugar 
that rotates to the left, but may be produced in the absence 
of albuminous substances (albumin, globulin, albumose, 
and peptone) by other bodies, especially /5-oxybutyric acid, 
glycuronic acid, cystin, and other compounds. 

It is characterized by being noncrystallizable when 
impure (although it crystallizes in long, wavy needles 
when pure), and by turning the plane of polarized light to 

^ Barfoed's Reagent : Dissolve one part of cupric acetate in 15 parts of 
water; to 200 c.c. of this solution add 5 c.c. of acetic acid containing 38 per 
cent, of glacial acetic acid ("Journ. f. prakt. Chem." [2], Bd. vi (1872), 
S. 344). 



168 ABNORMAL CONSTITUENTS OF URINE. 

the left instead of to the right. Its rotary power dimin- 
ishes as the temperature rises, while that of grape-sugar 
is independent of the temperature. Levulose reduces the 
salts of copper, although much more feebly than grape- 
sugar. 

There is no sure process known for the isolation of 
levulose. 

Detection. — Levulose is best detected by means of the 
polariscope, since it rotates the plane of polarized light to 
the left. It yields with phenylhydrazin an osazone (phenyl- 
levulosazone) that crystallizes in yellow needles w^hose 
melting-point is 150° C, while those formed from grape- 
sugar have a melting-point of 204° C. 

If the left-handed rotation is caused by substances other 
than levulose, by subjecting the urine to alcoholic fermen- 
tation the left-handed rotation disappears if due to this form 
of sugar, and persists if caused by other bodies. 



LAIOSE. 

(Leo's Sugar.) 

Laiose, Cfl^fi^, was first discovered by Leo,i who found 
it in the urine of 3 out of 21 severe cases of diabetes mellitus. 
These urines gave 1.2 to 1.8 per cent, more sugar by titration 
than by polarization. This sugar could not be isolated from 20 
liters of normal urine. 

Laiose is closely allied to levulose in that it rotates the plane 
of polarized light to the left, reduces alkaline solutions of the 
cupric salts, and combines with phenylhydrazin. It is not fer- 
mentable and does not have a sweet taste. The neutral pale- 
yellow syrup does not crystallize if kept for a year. It is 
readily soluble in water, moderately in methyl alcohol, spar- 
ingly in ethyl alcohol, and insoluble in ether and chloroform. 
It is completely precipitated by basic acetate of lead and 
ammonia. 

Isolation. — The urine is precipitated with basic acetate of 
lead, and the filtrate with ammonia. The second precipitate 
contains the laiose together with the dextrose. The precipitate 
is washed and decomposed with sulphuretted hydrogen. Since 
the filtered fluid becomes dark by evaporating in the air, Leo 
concentrated it by distilling in a vacuum, and finally drying 
over sulphuric acid. The syrupy residue is then dissolved in 
methyl alcohol, and the grape-sugar that has dissolved with it is 

1 Hans Leo, " Virchow's Archiv," cvii, 108, 1887. 



INOSITE. 169 

precipitated by a solution of baryta in methyl alcohol, sufficient 
to give a strongly alkaline reaction. It is quickly filtered, and 
the filtrate allowed to stand over sulphuric acid to remove the 
ammonia, by which procedure, besides the baric carbonate, the 
remainder of the barium compound of sugar is precipitated. 
Carbonic acid gas is passed through the filtrate to remove the 
excess of baryta, and the methyl alcohol is distilled off in a 
vacuum, the residue dissolved in water, and the baryta in solu- 
tion precipitated by sulphuric acid. 

Detection. — Urines that do not contain any more sugar by 
titration than by polarization need not be tested for this form 
of sugar. If the isolated substance is a reducing body, it is 
probably laiose. 



SUBSTANCES ALLIED TO SUGAR. 

INOSITE. 

(Muscle Sugar.) 

Inosite, CgH^^Og + 2H2O, is a rare constituent of the 
urine. It has occasionally been found in small quantity in 
diabetes mellitus, as an accompaniment of grape-sugar ; in 
the last stages of certain forms of chronic disease, particu- 
larly subacute glomerular and chronic diffuse nephritis ; 
and also after the ingestion of large quantities of water 
(Kiilz). It has also been found in phthisis, syphilis, and 
typhus fever. 

According to Neubauer and Vogel, inosite is not a 
sugar ; but from the experiments of Maquenne ^ it should 
be grouped among the compounds of the fat series, mannite. 

Inosite forms in cauliflower groups of crystals, and, at 
times, in single crystals that are three or four lines in length. 
It has a sweet taste, dissolves in 7. 5 volumes of cold water 
at 17° to 20° C, readily in hot water, and is slightly sol- 
uble in alcohol. It is very soluble in dilute or concen- 
trated acetic acid, and crystallizes more readily from these 
solutions than from water (Maquenne). It is insoluble in 
absolute alcohol and in ether. Its solutions are optically 
inactive, and it does not combine with phenylhydrazin, and 
is not fermentable by yeast ; it, however, undergoes lactic- 
and butyric-acid fermentation. Inosite does not reduce the 
cupric salts when boiled in the presence of an alkaline 

1 " Bull, dela Soc. Chim." [2], XLvn, 290; XLvni, 58, 1887 ; " Comptes 
Rendus," civ, 225, 297, and 17 19. 



170 ABNORMAL CONSTITUENTS OF URINE. 

hydrate, but not infrequently gives a greenish precipitate, 
which redissolves on cooling. 

Isolation. — The urine to be tested for inosite, after any 
albumin present has been removed, is first concentrated to 
one -fourth of its bulk, then completely precipitated with a 
solution of neutral acetate of lead, avoiding an excess, or 
with baryta water, filtered, and the warmed filtrate treated 
with subacetate of lead as long as any precipitate occurs. 
After twelve hours the subacetate precipitate that contains 
the inosite, together with lead oxide, is collected on a filter- 
paper, and after washing is suspended in water and decom- 
posed with sulphureted hydrogen. After standing a while 
a little uric acid first separates from the filtrate ; the fluid is 
filtered from it, then concentrated as much as possible, and 
while boiling treated with three or four times its volume of 
alcohol. If a heavy precipitate results that rapidly settles, 
the hot alcohoHc solution is simply poured off, but if a floc- 
culent nonadhesive precipitate occurs, the hot solution is 
filtered through a heated funnel and allowed to cool. If, 
after twenty-four hours, groups of inosite crystals have de- 
posited, they are filtered and washed with a little cold alco- 
hol. In this case it is advisable to dissolve the precipitate 
once more in as little boiling water as possible, and precipi- 
tate it a second time with three or four volumes of alcohol 
in order to avoid any loss of the inosite. If, however, no 
crystals of inosite have separated, ether is gradually added 
to the clear, cold, alcoholic filtrate until a milky cloudiness 
results on shaking thoroughly, and it is then allowed to 
stand twenty -four hours. Almost all of the inosite present is 
separated in the form of shining, pearly leaflets if too small 
an amount of ether has not been used (an excess does no 
harm). The separated inosite is recognized by the reactions 
I and 2, given below. 

Detection. — The urine should be free from albumin. 
The following tests (i and 2) depend upon the action of 
concentrated nitric acid which oxidizes inosite to rhodizonic 
acid. The carbohydrates do not give these reactions. 

I. If a fluid containing inosite is evaporated in a porce- 
lain dish to a few drops, and a small drop of Millon's 
reagent ^ is then added, a yellow precipitate is soon formed. 

1 Millon's Reagent : Dissolve one part of metallic mercury in two parts of 
ordinary nitric acid, evaporate to one-half volume, and add i ^ parts of water. 
After twenty- four hours the clear supernatant fluid is decanted from the basic salt. 



GLYCURONIC ACID. 171 

If this is spread out as much as possible on the edge of the 
dish and again gently warmed, there remains, as soon as the 
fluid is all evaporated, first a yellowish residue, which 
soon becomes red providing too much of the reagent has 
not been added. The color disappears on cooling, but re- 
appears upon the application of gentle heat. Starch, lactose, 
mannite, glycogen, uric acid, urea, taurin, and cystin do not 
give this red color ; albumin is colored red, and therefore, 
if present, must be previously separated. 

2. Evaporate the fluid containing inosite with concentrated 
nitric acid nearly to dryness, on a platinum dish, moisten 
the residue with a few drops of ammonic hydrate and a 
solution of calcium chloride. Then evaporate the mixture 
to dryness, and there appears a vivid rose-red color, which, 
according to Scherer,^ appears with even one milligram of 
inosite. 

GLYCURONIC ACID. 

Glycuronic acid, Cfl^fi^, is sometimes found in the urine, 
and is, above all, most likely to be mistaken for sugar. It 
probably occurs normally in very small amounts in the urine as 
combined glycuronic acid, coupled with potassium sulphate. 
It may appear in the urine in much larger quantities, particu- 
larly after the administration of chloral, butyl-chloral, chloro- 
form, turpentine, camphor, morphine, naphthalene, curare, and 
nitrobenzol, when it also exists in combination. After the ad- 
ministration of chloral it appears as urochloralic acid ; after cam- 
phor, as campho-glycuronic acid; after turpentine, as turpen- 
glycuronic acid ; after naphthalene, as naphthol-glycuronic 
acid, etc. It is said to occur in considerable quantities in the 
urine of apparently healthy people who have not a diabetic 
history. 

Glycuronic acid, when pure, is not crystalline, but is ob- 
tained only as a syrup. It dissolves in alcohol, is readily solu- 
ble in water, but insoluble in ether. Glycuronic acid itself is 
dextrorotatory, but when in combination, turns the plane of 
polarized light to the left. It is converted into saccharic acid 
by the action of bromine, and seems to occupy an intermediate 
position between this acid and gluconic acid, CgH^^C^^, obtained 
by the oxidation of glucose or cane sugar with chlorine or bro- 
mine. It reduces the salts of copper, bismuth, silver, and 
mercury, and does not undergo alcoholic fermentation with 
yeast. It gives a crystalline compound with phenylhydrazin. 

1 "Ann. d. Chem. u. Pharm.," Lxxxi, 375. 



172 ABNORMAL CONSTITUENTS OF URINE. 

Isolation. — Glycuronic acid is best isolated from the urine 
by the method of Schmiedeberg and Meyer, ^ as follows : 

Take a large quantity of urine and decolorize by means of 
animal charcoal. Then evaporate it to a syrup, and treat with 
a large quantity of damp barium hydrate, heating for some 
time over a water-bath. Extract with absolute alcohol, which 
leaves glycuronic acid and various other substances undissolved ; 
mix the residue with water and filter. Add more baryta to the 
filtrate, again filter, and evaporate the filtrate to a small volume 
over a water-bath. An amorphous barium precipitate separates, 
which is washed with water, and then decomposed by sulphuric 
acid. The barium sulphate is then filtered off, the filtrate evapo- 
rated down and dried in a vacuum, when crystals of the anhy- 
dride will be obtained. 

Detection. — If the urine reduces the salts of copper, and 
does not undergo alcoholic fermentation with yeast, and is 
dextrorotatory, glycuronic acid is probably present. 



CANE SUGAR. 

(Saccharose.) 

Cane sugar, 0^2^22^11' ^^ ^ ^^O' uncommon constituent of the 
urine. It has been found after the ingestion of large quantities 
of cane-sugar, but only in rare instances, and, therefore, is of no 
practical importance from a clinical standpoint. It occasionally 
appears in the urine from extraneous sources, particularly when 
the urine is transported in a bottle that is not clean or has con- 
tained simple syrup. It is sometimes added to the urine by the 
insane, or those persons who are disposed to deceive the physi- 
cian or chemist. 

Cane sugar, when pure, does not reduce the salts of copper, 
but, on account of the fact that the commercial article contains 
traces of glucose as an impurity, a reduction of the cupric oxide 
may follow the test. It crystallizes in prismatic form, and its 
aqueous solutions rotate the polarized light strongly to the right, 
-j- 73.8. When boiled with dilute hydrochloric or sulphuric 
acids, it undergoes the process of ^Hnversion " — that is. it takes 
up a molecule of water and is converted into dextrose and levu- 
lose, according to the following equation : 

Cl2^220ll + ^2^ == CgHjgOg + CgHj^Og. 

Dextrose. Levulose. 

On account of the strong rotation of levulose the solution 
now rotates to the left instead of to the right ; hence the term 
inversion. 

i^Zeitschr. f, physiol. Ch.," in, 422, 1879. 



PENTOSES.— ACETONE. 173 

Detection. — Traces of cane sugar may be overlooked in the 
ordinary analysis of the urine. When present in larger quanti- 
ties, the specific gravity is usually very high, even though the 
normal solids are not increased ; any glucose present is usually 
found to be in small quantities. The dextrorotatory polarization, 
which, after inversion, becomes levulorotatory, indicates the 
presence of cane sugar. 

PENTOSES. 

Pentoses (Cfl^fi^) were first found by Salkowski and Jastro- 
witz, 1 in the urine of persons addicted to the use of morphine. 
They were later found by Kiilz and Vogel ^ in the urine of those 
suffering from diabetes mellitus. 

They are nonfermentable, and on heating with dilute mineral 
acids yield furfurol, but no levulinic acid. They form osazones 
with phenylhydrazin (melting-point 159° C), are dextrorota- 
tory, and reduce alkaline solution of copper. 

Pentoses are present in vegetable food. They seem to be ab- 
sorbed by man, and utilized at least in part (Hammarsten). 
There are two important pentoses — /. e. , arabinose and xylose. 

Arabinose (pectin sugar) is dextrorotatory, a (D) = -|~^o4° 
to 105°. Its osazone melts at 157° to 158° C, and 10 c.c. of 
Fehling's solution are reduced by 43 milligrams of arabinose 
(Hammarsten). 

Xylose (wood sugar) is only feebly dextrorotatory, a (D) = 
-|-i8.i°. Its osazone melts at 159° to 160° C. 

Detection. — Pentoses are detected (i) by their reducing 
action on alkaline solutions of copper ; ( 2 ) by being nonfer- 
mentable ; (3) by the melting-point of their osazones ; (4) by 
their spectroscopic appearance — /. e. , two absorption bands be- 
tween D and E. It should be borne in mind that glycuronic 
acid has the same spectrum as the pentoses. In a mixture of 
pentoses and glycuronic acid the separation is made, according 
to Kiilz and Vogel, ^ by extracting the osazones of these two sub- 
stances with water at 60° C, which dissolves the pentosazone ; 
filter while hot, and allow to cool. The pentosazone separates 
upon cooling. 

ACETONE. 

Acetone is a volatile compound frequently found in large 
amounts in the urine under certain diseased conditions. 
According to v. Jaksch, de Boeck, and A. Slosse, normal 

1 E. Salkowski u. M. Jastrowitz, " Centralbl. f. d. med. Wissensch. ," 1892 ; 
Salkowski, " Berliner klin. Wochenschr. ," 1895. 

2 E. Kiilz u. J. Vogel, " Zeitschr. f. Biologie," 22, 1895. 

3 /did. 



174 ABNORMAL CONSTITUENTS OF URINE. 

urine contains traces of acetone (o. i gram in twenty-four 
hours — "physiological acetonuria "). Le Noble claims, 
however, that this body is only found in the urine of 
healthy persons after the use of alcohol and food rich in 
proteid matter. 

Acetone, CgHgO, is the typical member of the group 
known as ketones, and may be prepared artificially by the 
dry distillation of calcium or barium acetate. It may be 
obtained in considerable quantities by distillation of the 
urine or the blood of certain diabetic individuals. The 
peculiar fruity, sweet odor frequently noticed in the breath 
and in the urine of diabetic subjects is due to acetone. It 
is a volatile, colorless liquid, of a specific gravity of 0.792, 
boiling at 56.5° C, soluble in water, and characterized by 
an ethereal or fruity odor. The principal source of acetone 
is the decomposition of the proteids of the body as well 
as those taken as food (v. Jaksch). Some writers believe, 
on the contrary, that it is the decomposition of the fats, and 
not the proteids, which constitutes the chief source of 
acetone. 

Clinical Significance. — The condition of acetonuria is 
divided by v. Jaksch, according to cause, into : (i) Febrile 
acetonuria (scarlet fever, typhoid fever, pneumonia, measles, 
smallpox, etc.) ; (2) diabetic acetonuria ; (3) acetonuria 
accompanying certain forms of cancer independent of inani- 
tion ; (4) acetonuria of starvation, seen especially in cases of 
gastric ulcer and following the use of rectal feeding ; (5) the 
production of acetone in psychoses ; (6) acetonuria as an ex- 
pression of autointoxication ; (7) acetonuria in derangements 
of digestion ; (8) acetonuria in chloroform narcosis. The 
most common of these forms is febrile acetonuria. It is seen 
in children as well as jn adults, and does not belong to any 
particular fever. In diabetes the appearance of acetone in 
the urine indicates an advanced stage of the disease. The 
ingestion of an abundance of nitrogenous food tends to the 
production of acetonuria. Thus it is that the urine of dia- 
betics often contains a larger amount of acetone after elimi- 
nating starches and sugars from the diet, and restricting it 
chiefly to nitrogenous substances. Acetonuria existing 
alone (autointoxication with acetone) tends to a favorable 
termination. Of greater importance are those cases in 
which much acetone is found as an accompaniment of grave 
symptoms of cerebral irritation. 



ACETONE. 175 

Detection. — Legal' s Test. — This is a rough test, but is 
of service on account of being easy of application. 

One-fourth of a test-tube of urine is treated with a few 
drops of a freshly prepared and somewhat concentrated 
solution of sodium nitroprusside, a few drops of acetic 
acid are added to prevent the reaction with kreatinin, and 
the mixture is then rendered alkaline with ammonic or sodic 
hydrate. The mixture gradually develops a red color, 
which increases to a deep purple-red color. In the absence 
of acetone the red or purple-red tint does not form. 

For purposes of greater accuracy it is necessary to distil 
the urine (500 to 1000 c.c), after the addition of a little 
phosphoric acid (i gram per liter), to prevent the evolution 
of gases ; the first 10 to 30 c.c. of the distillate are used 
for the following tests : 

Lieben's Test. — A few cubic centimeters of the distillate 
are treated with several drops of a dilute solution of iodo- 
potassic iodide and sodic hydrate. In the presence even 
of traces of acetone, a precipitation of iodoform in crys- 
talline form occurs, which may be readily recognized by 
its odor. 

Quantitative Estimation of Acetone. — The method of 
Messinger, as modified by Huppert, is best adapted to the esti- 
mation of acetone in urine, and is based upon the observation 
of Lieben, that acetone gives rise to the formation of iodoform 
when treated with iodine in an alkaline solution. If, then, a 
solution of acetone be treated with a known amount of iodine, 
the quantity present is determined by retitrating the iodine that 
was not used in the formation of iodoform. 

Solutions Required. — (i) Acetic acid (50 per cent, solution) ; 
(2) sulphuric acid (12 per cent, solution); (3) sodic hydrate 
solution (50 per cent.) ; (4) a decinormal solution of iodine ; 
(5) a decinormal solution of sodium thiosulphate. 

Process. — One hundred cubic centimeters of urine, or less if 
much acetone be present as determined by Legal' s test, are 
treated with 2 c.c. of the acetic acid solution, and distilled until 
seven-eighths of the total amount has passed over. The dis- 
tillate is received in a retort that is connected with a bulb appa- 
ratus filled with water. As soon as seven -eighths of the urine 
has distilled over, a small amount of the distillate of the 
remainder is tested for acetone by Lieben's method. Should a 
positive reaction be obtained, it will be necessary either to 
repeat the entire process with less urine, diluted to about 200 
c.c, or to add about 100 c.c. of water to the residue and to 



176 ABNORMAL CONSTITUENTS OF URINE. 

distil until all the acetone has been driven over. The distillate 
is then treated with i c.c. of the sulphuric acid, and redistilled. 
The addition of the acetic acid and of the sulphuric acid, respect- 
ively, serves the purpose of holding back the phenol and the 
ammonia. Should the first distillate contain nitrous acid, 
which may be recognized by the addition of a little starch-paste 
containing a trace of potassium iodide, when the solution will 
turn blue, this is removed by adding a little urea. The second 
distillate is received in a bottle provided with a well-ground 
glass stopper, and holding about one liter. To prevent the 
escape of acetone, the glass stopper is replaced by a doubly per- 
forated cork, through which two glass tubes pass, one to the 
distilling apparatus, the other to the bulb apparatus. The dis- 
tillate is then treated with a carefully measured quantity of the 
decinormal solution of iodine — about lo c.c. for each loo c.c. 
of urine used — and sodic hydrate solution, which should be 
added drop by drop until the blue color has disappeared and 
the iodoform separates out. To this end a slight excess of the 
solution must be added. Should ammonia be present, a blackish 
cloud will be observed at the zone of contact of the sodic hydrate 
and the iodine solution, and it will be necessary to repeat the 
entire process. The bottle is closed and shaken for about one 
minute. The solution is then acidulated with concentrated 
hydrochloric acid, when the mixture assumes a brown color if 
iodine be present in excess. If this does not occur, more of the 
iodine solution must be added, and the process repeated until 
an excess is present. The excess is then retitrated with the 
thiosulphate solution until the solution presents a faint yellow 
color. A few cubic centimeters of starch solution are then 
added, and the titration continued until the last trace of blue 
has disappeared. The number of cubic centimeters employed 
in the titration is finally deducted from the total amount of the 
iodine solution added, and the result multiplied by 0.967. 
The figure thus obtained will then indicate, in terms of milli- 
grams, the amount of acetone contained in the 100 c.c. of urine, 
as I c.c. of the thiosulphate solution is equivalent to i c.c. of 
the iodine solution, or to 0.967 milligrams of acetone. 



DIACETIC ACID, 

Diacetic acid, also termed aceto-acetic or ethyl -diacetic 
acid, CgH^gOg, sometimes appears in the urine. Its pres- 
ence must always be regarded as abnormal. Urine con- 
taining diacetic acid is always rich in acetone, for which 
diacetic acid is often mistaken. These two bodies exist in 
the urine independently, although by the action of alkalies 



DIACETIC ACID. 177 

diacetic acid is readily converted to acetone, alcohol, and 
CO.,, as shown by the following: 

CeH^oOs + HP = CgHgO + QHgO + CO^ . 
Diacetic acid. Acetone. Alcohol. 

Whether a similar decomposition takes place in the blood 
remains still an open question. 

Diacetic acid is a colorless liquid, which gives a charac- 
teristic Bordeaux-red color with a solution of ferric chloride. 
But this color with ferric chloride may be produced by the 
presence of other substances in the urine, such as salicylic 
acid, carbolic acid, antipyrin, thallin (Legal and Hammar- 
sten) ; also acetic and formic acids, sulpho- (thio-) cyanates, 
and /5-hydroxybutyric acid. Diacetic acid is distinguished 
from these substances by the fact that, if the urine be pre- 
viously boiled, diacetic acid does not give the ferric chloride 
reaction, while the other substances continue to give the 
Bordeaux-red color as before. Furthermore, that salicylic 
acid, carbolic acid, etc., are not extracted from the urine by 
ether, whereas diacetic acid is soluble in ether. 

Clinical Significance. — As already mentioned, the pres- 
ence of diacetic acid in the urine (diaceturia) is always 
pathologic, and should in general be considered a serious 
symptom. Diacetic acid is frequently found in the urine in 
diabetes mellicus, in fevers, and also idiopathically as a form 
of autointoxication (diacetemia). It is of common occur- 
rence in the urine of children as a concomitant of fever 
(v. Jaksch), and is then generally devoid of serious impor- 
tance ; but in children or adults suffering from diabetes it is 
a symptom of grave import. Diaceturia is most common 
in the advanced stages of diabetes mellitus, and particularly 
in children and persons under the age of thirty. The oc- 
currence of this symptom may be looked upon as a very 
probable forerunner of diabetic coma and rapid death. The 
author's experience has led him to make an unfavorable prog- 
nosis in all cases of diabetes mellitus (under thirty years of 
age) in which the urine contains diacetic acid. 

The form of autointoxication of which diaceturia is the 
chief index is usually rapidly fatal, being accompanied by 
such symptoms as vomiting, dyspnea, jactitation, and coma, 
without evidence of any other pathologic process. 

Detection. — The process suggested by v. Jaksch is most 
reliable, and is as follows : To the urine a fairly concen- 

12 



178 ABNORMAL CONSTITUENTS OF URINE. 

trated solution of perchloride of iron is cautiously added, 
and if a phosphatic precipitate forms, this is removed by 
filtration, and more of the perchloride of iron solution sup- 
plied. If the Bordeaux-red color appears, one portion of 
the urine is boiled, while another portion is treated with 
sulphuric acid and extracted with ether. If now the urine 
that has been boiled gives no reaction with the perchloride 
of iron solution, while the ethereal extract shows a claret- 
red color with the iron solution, diacetic acid is probably 
present, particularly if, at the same time (on testing the 
urine directly and its distillate), it is found to be rich in 
acetone. 

The urine to be tested should be perfectly fresh, for the 
reason that in a urine that has begun to decompose the 
diacetic acid takes up a molecule of water and splits into 
acetone, alcohol, and carbon dioxide. 



/3-OXYBUTYRIC ACID. 

(QH3O3.) 

/?-oxybutyric acid not infrequently appears in the urine 
as an accompaniment of diacetic acid and acetone. It forms 
with aqueous vapor an odorless, colorless, transparent, non- 
volatile syrup, which rotates the plane of polarized light 
toward the left. It is monobasic, and its salts are readily 
soluble in water ; it is only moderately soluble in absolute 
alcohol, and is precipitated from its solutions by ether. It 
gives no reaction with a solution of ferric chloride. It is 
easily convertible into acetone and diacetic acid by oxidiz- 
ing agents. 

Although /3-oxybutyric acid is usually found as an ac- 
companiment of acetone and diacetic acid, the presence of 
the two last-named substances does not necessarily indicate 
the presence of /5-oxybutyric acid. 

Clinical Significance. — /5-oxybutyric acid is met with in 
large amounts in the urine of those suffering from the se- 
vere forms of diabetes mellitus ; in small amounts in scurvy, 
scarlet fever, and measles (Minkowski, E. Kiilz), but not in 
other febrile diseases (Minkowski). It has also been found 
in the urine of starving insane patients, in that of cancer 
patients dying from coma (Klemperer, Lorenz), and in indi- 
viduals living on an exclusive meat and fat diet. /5-oxy- 
butyric acid is of greatest importance in severe cases of 



BILE. 179 

diabetes mellitus, in which it is probably the cause of the 
acid intoxication which usually precedes and accompanies 
diabetic coma. According to Herter, ^ the persistent excre- 
tion of more than 25 grams of /5-oxybutyric acid indicates 
impending coma. 

Isolation. — The isolation of /5-oxybutyric acid is rather 
difficult, but the process advised by Magnus-Levy 2 may 
be used. 

Process. — Take 400 c.c. of the urine, add 15 or 20 grams 
of ammonium sulphate, and evaporate to about 80 c.c. 
Filter, and treat an ahquot portion of the filtrate correspond- 
ing to 250 c.c. of the urine with dilute sulphuric acid which 
has been previously saturated with ammonium sulphate. 
Shake this acid mixture for about fifteen minutes with 400 
c.c. of ether ; make at least eighteen extractions, and em- 
ploy 400 c.c. of ether for each extraction. Wash the ether 
used for each extraction "with 25 c.c. of water, and finally 
unite the ethereal extracts and distil. The /5-oxybutyric 
acid, together with hippuric acid, volatile fatty acids, and 
an unidentified acid-equivalent, is contained in the clear dark 
brown liquid that remains. This fluid is then examined 
by means of the polariscope. 



BILE. 

Of the constituents of bile, the biliary pigments and 
acids chiefly concern us here. Another constituent of bile 
— viz., cholesterin — has never yet been found in the urine 
in jaundice, but has been met with in considerable quantities 
in other connections. 

BILIARY PIGMENTS. 

A urine containing more than a minute trace of bile 
is always abnormally colored. The chief unaltered biliary 
pigment is bilirubift, which is an intermediate product 
in the body between hemoglobin and urobilin. (See 
p. 92.) When bilirubin (orange-yellow) becomes oxi- 
dized, either by exposure to the air or by reagents, the 
first and most important oxidation product is biliverdin 
(green) ; then follow the less important products, bilicyajiin 
(blue), bilifiiscin, biliprasin, and finally choletelin {?'). Bili- 
rubin is in the urine in a free state ; but in biliary calculi. 

1 "Journ. Exper. Med.," Nov., I90i,p. 617. 

2 Magnus- Levy, " Centralbl. f. innere Med.," Bd. xlv, S. 390. 



180 ABNORMAL CONSTITUENTS OF URINE. 

in which it is often present in abundance, it exists as a cal- 
cium compound — bilirubin calcium. 

The color of a bile-containing urine is either greenish-yel- 
low, yellowish-brown, deep brown, greenish-brown, or, on 
standing exposed to the air, may be nearly pure green. On 
shaking the urine it gives a persistent greenish-yellow or yel- 
low froth or foam. Furthermore, if a piece of filter-paper or 
linen be moistened with such urine, it retains a permanent 
yellow color on drying. A jaundiced urine almost invari- 
ably contains an excess of urobilin and indoxyl. A urine 
from which the bile has recently disappeared is usually 
highly colored, due to the large excess of urobilin. 

A bile-containing urine is always albuminous. The 
chief proteid appears to be nucleo-albumin, which is 
usually accompanied by traces of serum albumin. In this 
connection it is noteworthy that the nitric acid test for 
albumin can not be satisfactorily used for the detection of 
slight traces, on account of the amount of coloring-matter 
set free by the acid, thus obscuring a faint zone of albumin. 
For this reason, therefore, in a urine containing much bile, 
the heat test for albumin is preferable. The sediment 
usually contains a large number of renal epithelial cells, 
which are more or less colored by the bile pigment. Not 
infrequently, they have attached to their surfaces stellate 
clusters of bilirubin crystals, which have a yellowish-brown 
color ; also small, irregular, brown, bilirubin granules. (See 
p. 226.) The sediment also contains renal casts and abnor- 
mal blood globules, free and adherent to casts, the result of 
the irritation of the kidneys by the bile. If more than a 
mere trace of bile pigment be present in the urine, the organ- 
ized elements of the sediment are invariably stained yellow 
or yellowish-brown. 

Clinical Significance. — Bile pigments occur in the urine 
in every case of jaundice — in other words, in every case in 
which there is an obstruction to the outflow of bile from 
the bile-ducts (Jiepatogenous icterus). Thus they are found 
in a variety of pathologic conditions of the liver, of which 
the most common are catarrhal jaundice, obstruction in the 
common bile-duct by biliary calculi, cancer, and cirrhosis 
of the liver. They may also appear in the urine in cases 
of destruction of the red blood globules, as in severe infec- 
tious conditions, phosphorus-poisoning, etc. (liematogenous 
icterus ). Bile pigments often make their appearance in the 



BILE. 181 

urine before there is much coloration of the conjunctivae, or 
any \'ellow color in the skin. 

Detection. — Marechalt's Test. — Take about one finger- 
breadth of an alcoholic solution of iodine (not too strong) 
in a test-tube, and underlie with urine by allowing it to flow 
down the side of the inclined test-tube from a pipette placed 
above the level of the iodine. If biliary pigments are 
present, a green color appears just below the point of con- 
tact of the two fluids, and remains for some time, even for 
twenty -four hours. In this test the possibility of confound- 
ing with indoxyl is said to be excluded. 

Gmelin's Test. — This test is performed in two ways : 

1. A quantity of urine is placed in a wine-glass, and a 
small quantity of concentrated nitric acid is allowed to flow 
carefully down the side of the wine-glass to underhe the urine, 
as described in the nitric acid test for albumin. If biliary 
coloring-matters are present, at the point of union between 
the urine and the acid a play of colors will very soon 
appear, which, if typical, should be green, blue, violet, red, 
and yellow or yellowish-green, in the order named. Often, 
however, one or more colors are wanting. The green is 
most constant, the first green being indispensable to prove 
the presence of bile ; but violet, shading into red and yellow, 
is also very constantly seen. The other colors may be pro- 
duced by other coloring-matters, especially indoxyl. 

2. The test can also be appHed by placing a drop of the 
suspected urine on a porcelain plate, and allowing a drop 
of the fuming nitric acid, which has been placed adjacent, to 
gradually mingle with the urine. The same play of color 
occurs. 

Another method consists in precipitating the urine with 
a small amount of milk of lime. A small portion of this 
precipitate is then treated with a drop of concentrated nitric 
acid, and if bile pigments are present, a play of colors, like 
that seen in Gmelin's test, occurs. 

The two tests for biliary pigments just described are quite 
satisfactory, providing the urine contains a large amount of 
bile, but they are far from conclusive when the urine con- 
tains minute traces of biliary pigments. Various other tests 
for bile pigments have been advised, but all possess greater 
shortcomings than Marechalt's or Gmelin's tests, and many 
of them are valueless. In the hands of the writer Mare- 
chalt's test is the most serviceable of all tests, especially 



182 ABNORMAL CONSTITUENTS OF URINE. 

when applied in the manner previously outlined. It is to be 
said, however, that a normal urine often reacts with iodine 
so as to suggest a trace of bile when it is evident that no 
bile pigments are present. It is certain that this subject 
needs further investigation in order to be able to demon- 
strate satisfactorily the presence of traces of bile pigments 
in urine. 

BILIARY AQDS. 

Any interference with the discharge of bile from the liver 
or common bile-duct results in the passage of the bile con- 
stituents into the blood and their elimination by the urine 
{Jiepatogenous icterus). But bile pigments may also pass into 
the urine under other circumstances, especially when there 
is destruction of the red blood-corpuscles through poisoning 
by ether, chloroform, arseniureted hydrogen, phosphorus, 
and in grave infectious diseases. In this second form of 
icterus the blood coloring-matter appears to be transformed 
into bile pigment elsewhere than in the liver, possibly in the 
blood, and thus it is that we have the so-called hematogenous 
icterus. Only the bile pigments appear in the urine in these 
cases, while in hepatogenous icterus the urine contains the 
bile pigments and bile acids at the same time (Ley den). 
This arbitrary distinction, however, can not be fully main- 
tained in all cases. It is certainly true that the presence 
of more than mere traces of bile acids in the urine indicates 
the existence of hepatogenous jaundice, but cases of absorp- 
tion icterus undoubtedly occur in which no bile acids can be 
detected in the urine. 

According to Dragendorf, Vogel, and Oliver, traces of 
bile acids occur in normal urine, but Hoppe-Seyler and 
Udranszky both hold the opposite view. This question 
must be considered unsettled until confirmatory evidence 
bearing upon one or the other view is at hand. 

All bile acids can be conveniently divided into two groups 
— the glycocholic and the taurocliolic acid groups. The glyco- 
cholic acids contain nitrogen, but are free from sulphur, 
and can be split, with the addition of water, into glycocoll 
and an acid free from nitrogen — cholic acid. The tauro- 
cholic acids contain nitrogen and sulphur, and are split, 
with the addition of water, into taurin, which contains sul- 
phur and cholalic acid. The existence of different glyco- 
cholic and taurocholic acids depends on the fact that there 



BILE. 183 

are several cholalic acids. These two groups of acids exist 
in the urine chiefly as salts of sodium. 

Clinical Significance. — -As already intimated, bile acids 
are most commonly found in the urine in cases of obstruc- 
tive jaundice — that is, in the hepatogenous form, and not gen- 
erally present in the hematogenous fornj of icterus. This very 
general rule, however, is subject to much variation, and, 
therefore, the determination of the presence of bile acids 
can not be considered especially diagnostic of the existence 
of hepatogenous jaundice. They are present in the urine 
of hepatic congestion, cirrhosis, and hepatic tumors ; also 
in carcinoma and severe acute bilious attacks. They have 
also been found in anemia, hemoglobinuria, scurvy, and 
splenic leukemia. They are much less common in the 
urine in amyloid infiltration of the liver. 

Tests for bile acids are not usually made in the routine 
analysis of urine. In fact, for purposes of diagnosis, the 
detection of bile pigments is generally sufficient. It is impos- 
sible to apply satisfactorily the ordinary test — Pettenkofer's 
— for bile acids directly to the urine ; they must, therefore, 
be isolated. 

Isolation. — The simplest method of obtaining the biliary 
acids is the one suggested by Dr. Tyson, ^ and is as fol- 
lows : " Six or eight ounces (i8o to 240 c.c.) of the sus- 
pected urine are evaporated to dryness over a water-bath. 
The residue thus obtained is treated with an excess of abso- 
lute alcohol, filtered, and the filtrate treated with an excess 
of ether (12 to 24 times its bulk), by which the bile acids, if 
present, are precipitated. These are then removed by fil- 
tration, and redissolved in distilled water. The solution is 
then decolorized by passing through animal charcoal, and 
the resulting colorless fluid subjected to Pettenkofer's test." 

According to Hoppe-Seyler, the bile acids can be sepa- 
rated from the urine in the following manner : Render 
the urine alkaline with ammonic hydrate, and precipitate 
directly with basic acetate of lead ; wash the precipitate 
with water, dry by gentle heat, heat several times with 
absolute alcohol, and filter while hot. To the alcoholic 
solution of lead salts of the bile acids add a few drops of 
sodic hydrate and evaporate to dryness. Extract the 
residue with absolute alcohol by the aid of heat ; evapo- 

1'* Philadelphia Medical Times," July 5, 1873. 



.184 ABNORMAL CONSTITUENTS OF URINE. 

rate the solution to a small volume, and shake with an 
excess of ether, whereby the biliary salts are separated 
as an amorphous precipitate. Filter, dissolve the precipi- 
tate in distilled water, and apply Pettenkofer's test. 

Dragendorff has shown that the bile acids can be extracted 
from urine that has been acidulated with hydrochloric acid 
by shaking with chloroform. 

If ox bile be added to urine, Pettenkofer's reaction can 
generally be demonstrated without separating the bile salts 
as just indicated, providing, however, the color of the urine 
used is normal or pale, and not high. 

Detection. — Pettenkofer's Test for Bile Acids. — The 
test, as usually applied, is as follows : 

Process. — Bile, which may be considerably diluted, or a 
dilute solution of bile salts or acids, is mixed in a porce- 
1am dish with a few drops of a lo per cent, solution of 
cane sugar. Concentrated sulphuric acid is then added to 
the mixture, with constant stirring, to an extent not ex- 
ceeding two-thirds of its volume, the addition of the acid 
being so regulated that the temperature of the mixture is 
not allowed to rise above 70° C. A brilliant cherry-red 
changing to a reddish-purple color soon makes its ap- 
pearance. On standing for some time the color becomes 
darker and assumes more of a blue tint. The reaction 
may also be obtained by the addition of first the acid and 
then the sugar solution. The success of the test depends 
upon keeping the temperature of the mixture below 70° C. 
(a cold water- bath may be used), and the avoidance of any 
excess of sugar, which, by being charred by the acid, gives 
a brown color and masks the typical purple. To avoid 
this, Drechsel recommends the use of phosphoric acid 
(5 of the glacial acid to i of water) instead of sulphuric acid. 
In this case the solution must be heated by immersion in 
boiling water. 

According to Schenk,i if the typical purple solution is 
diluted with alcohol, it shows with the spectroscope a char- 
acteristic absorption spectrum, consisting of two absorption 
bands, one between D and E, bordering on E, and a second 
between E and F, adjoining F. 

Pettenkofer's reaction depends upon the presence of 
cholalic (or cholic) acid, a constituent of the bile acids ; also 

1 " Jahresber. f. Tliier-Ch.," ii, 232. 



BILE. 185 

upon the formation of fiirfiirol (also known as furfuralde- 
hyde) which results from the action of the sulphuric acid 
upon the sugar, the characteristic color arising from the in- 
teraction of the furfurol with the cholalic acid. 

This test is far from satisfactory when applied directly to 
the urine, even when the bile acids are present in consid- 
erable amount, since, on the one hand, urinary pigments 
and other substances are charred by the sulphuric acid, 
thus interfering with the brilliancy of the reaction ; and, 
secondly, if the urine contains proteids, cholesterin, amyl 
alcohol, and various other substances, a purple color is pro- 
duced which closely resembles that due to bile acids. 

Oliver's Peptone Test. — This test is based on the physi- 
ologic fact that, when the products of gastric digestion, pep- 
tone and parapeptone, which pass from the stomach in an acid 
medium, meet with the bile in the duodenum, they are precipi- 
tated. So, too, albuminous urine, or urine charged with pep- 
tone, is precipitated by a solution of bile salts, — sodium glyco- 
cholate or taurocholate. Thus an acid solution of peptone is 
recommended and is prepared as follows : 

Pulverized peptone (Savary and Moore), 30 grains; salicylic 
acid, 4 grains ; acetic acid, 30 minims ; and distilled water up 
to 8 fluidounces. Filter until a clear filtrate is obtained. 

Process. — To 60 minims of this test solution add 20 minims 
of perfectly clear urine which has been previously rendered nor- 
mally acid if alkaline, and which has been reduced to a specific 
gravity of 1008. If the proportion of bile salts be normal or 
subnormal, no immediate reaction occurs, but in a short time a 
mere tinge of milkiness appears. If in excess, a distinct tur- 
bidity promptly appears, becoming more intense in a minute or 
two, the degree of opacity being directly proportionate to the 
amount of bile acids present. On agitation the opalescence 
diminishes, and may finally disappear, but is restored on adding 
more of the test solution. 

Approximate Quantitative TEST.^This is based upon a 
permanent standard of opacity provided by mixing equal pro- 
portions of the test solution and normal urine reduced to the 
specific gravity of 1008. To 60 minims of the test solution 
add the suspected urine diluted to a specific gravity of 1008, 
usually 10 to 20 minims at a time, allowing a minute to elapse 
after each addition, until the opacity induced is exactly equal 
to or slightly exceeds that of the standard, the tubes being held 
to the light, shaded by a dark background. If 50 or 60 minims 
bring up the opacity to that of the standard, the proportion of 
bile salts does not exceed the normal. Any smaller quantity 



186 ABNORMAL CONSTITUENTS OF URINE. 

required indicates an excess, while the smaller the amount 
needed, the larger the proportion of bile salts present. 

OLIVER'S STANDARD TABLE. 



Minims. 


Urine. 


Drops. 


Perc 

1 


entage of Increase over 
the Normal Standard. 


I 


or 


2 


^ 


6000 


2 


or 


4 


= 


3000 


3 


or 


6 


= 


2000 


4 


or 


8 


= 


1500 


5 


or 


10 


= 


1200 


lO 


or 


20 


= 


6CK) 


15 


or 


30 


= 


400 


20 


or 


40 


= 


300 


25 


or 


50 


= 


240 


30 


or 


60 


= 


100 


35 
40 


or 
or 


70 
80 





83 

66 


45 


or 


90 


= 


50 



This test, according to Dr. Oliver, is so delicate that one 
part of bile salts can readily be detected in 18,000 to 20,000 
parts of a solution of sodium chloride. An increase over 700 
per cent, beyond the normal is rarely encountered. Oliver has 
yet to find anything that interferes with this test for bile acids 
in the urine. 

Dr. Oliver has also devised a peptone test-paper that he con- 
siders permanent, reliable, and convenient for use. 

EHRLICH^S DIAZO REACTION. 

This reaction was first described by Ehrlich ^ in 1882. 
It depends upon the peculiar color produced in the urine 
(and more particularly in the foam) by the action of diazo- 
benzol-sulphonic acid upon certain unknown substances in 
the presence of an excess of ammonic hydrate. 

The following solutions are necessary for the reaction : 

Solution A. 

Sulphanilic acid (saturated aqueous solution) . 200 c.c. 
Hydrochloric acid (concentrated) ...... 10 " 

Solution B. 

Sodium nitrite I " 

Distilled water 200 " 

These solutions {A and E) are to be kept separate, in 
well-stoppered bottles, and preferably in a dark place. It 
is necessary to have the sodium nitrite solution as fresh as 
possible, and, since it decomposes in the course of a few 



1 a 



Zeitschr. f. klin. Med.," iv, 285-288. 



EHRLICH'S DIAZO REACTION. 187 

weeks, it is advisable to keep only a small quantity of it 
on hand. 

Method of Applying Test. — Take in a test-tube a mix- 
ture of 40 parts of solution A and i part of solution B ; 
add an equal volume of urine ; shake the whole mixture 
thoroughly, and allow an excess of ammonia hydrate to 
run slowly down the side of the tube. If the diazo reac- 
tion be present, the foam will be colored pink, and that 
portion which is acted upon by the ammonic hydrate will 
have a crimson color. When the test-tube is inverted, the 
entire column of liquid in the tube will be found to have a 
crimson color, while the foam still remains pink. 

Ehrlich found that this reaction was almost constantly 
present in the urine of typhoid fever. He also obtained 
the reaction in the urine of a variety of other diseases, 
mostly acute febrile diseases, but in these its occurrence 
was not constant. He, therefore, called attention to the 
value of the diazo reaction as an aid in the diagnosis of 
typhoid fever. 

Since the discovery of this peculiar reaction in the urine 
considerable discussion has arisen as to its clinical value in 
connection with the diagnosis of typhoid. It is safe to 
say that the reaction, as ordinarily applied, has met 
with much disfavor, owing partly to the fact that it is 
frequently obtained in the urines of a number of other dis- 
eases, such as pulmonary phthisis, pneumonia, pleurisy, 
scarlet fever, diphtheria, measles, erysipelas, acute miliary 
tuberculosis, syphilis, carcinoma, puerperal septicemia and 
other septic conditions, acute and chronic rheumatism, etc., 
and partly on account of the failure of some observers to 
follow the methods laid down by Ehrlich. 

Dr. Charles L. Greene, of St. Paul, Minn., who has 
made a very careful study ^ of this subject, has found 
that much more satisfactory results are obtained by 
modifying the proportions of solutions A and B. He, 
therefore, recommends the use of a test solution, which 
shall consist of 100 parts of solution A and I part of 
solution B, instead of 40 parts of A and i part of B as 
ordinarily used. In a study of 315 cases representing 
many of the common forms of disease he obtained by 
means of this modified test solution characteristic reactions 

1 *' Medical Record," Nov. 14, 1896. 



188 ABNORMAL CONSTITUENTS OF URINE. 

in only five diseases : /. e., typhoid fever, 95 per cent. ; 
pneumonia, 9 per cent. ; carcinoma, 50 per cent. ; pulmon- 
ary phthisis, 12.5 per cent.; and septicemia, 75 percent. 
He firmly believes that all cases of severe typhoid will 
show a diazo reaction if the test is properly applied during 
the height of the disease — that is, between the tenth and 
eighteenth days. 

Von Jaksch,^ on the other hand, believes that the so- 
called diazo reaction is always due to. the presence of ace- 
tone, and he considers the reaction rather an uncertain test 
for acetone than a test for anything else. 

The author can recommend Greene's modified test solu- 
tion, since by its use positive reactions are obtained in a 
much smaller number of diseases than by the use of the 
original Ehrlich solution. However, he can not agree with 
Greene as to its diagnostic value in typhoid, owing to the 
fact that in some cases of this disease, especially the milder 
forms, no characteristic reactions can be obtained at any 
time during the disease. It is certain that many of the 
urines that show this reaction contain acetone, but further 
investigation is necessary to prove that the so-called diazo 
reaction is directly or indirectly due to acetone. 



VARIOUS METALLIC AND NONMETALLIC SUBSTANCES, 

Various metallic substances, notably lead, arsenic, and 
mercury, are eliminated in the urine, and, when suspected, 
should be carefully sought for. 

Arsenic may be absorbed in either small or large amounts, 
and is quite readily eliminated in the urine without the aid 
of drugs. It is, to a slight degree, cumulative — that is, 
sufficient arsenic may be absorbed in three or four days' 
time to require from sixty to ninety days for its complete 
elimination. 

Lead is usually absorbed in very small quantities, and 
the cause of its very slow elimination from the body is 
probably its accumulation in the system as a fixed con- 
stituent of the tissues. The natural channel of elimination 
is by way of the kidneys, and in order that it should become 
a constituent of the urine it must first be converted into a 

^ Von Jaksch, "Clinical Diagnosis," 1897, p. 375. 



METALLIC SUBSTANCES. 189 

soluble salt of lead. This is best effected by giving potas- 
sium iodide, which combines with the lead, forming iodide 
of lead, and is eliminated by the kidneys. Even after 
giving potassium iodide, and under the most favorable 
conditions, only minute traces of lead are eliminated in 
twenty-four hours. Therefore, a large quantity of urine 
is required for the analysis, and every precaution taken to 
prevent accidental contamination. 

Analysis. — The first step in the analysis for either ar- 
senic or lead is (i) the destruction of the organic matter of 
the urine, and the addition of sulphuric acid for the purpose 
of driving off the nitric acid, thus leaving the residue in the 
form of sulphates ; and (2) the application of independent 
tests for either lead or arsenic as the case may be. 

1. Destruction of Organic Matter. — Take at least one 
liter of urine in an evaporating dish, and evaporate to dry- 
ness over a water-bath. Add to this residue about 1 00 c.c. 
of concentrated nitric acid (C. P.), and continue the heat 
until the acid has evaporated, when a yellow cake remains. 
Transfer this yellow mass — nitrates and nitro-compounds — 
to a crucible by means of a porcelain spatula, heat with a 
Bunsen flame until the mass ignites, and continue the heat 
until a white residue remains. Cool ; add 10 to 20 c.c. of 
concentrated sulphuric acid (C. P.), and heat until all of the 
nitric acid has been expelled — that is, until the red fumes 
disappear and dense white fumes are evolved. Cool, and 
then add from 25 to 50 c.c. of distilled water, and filter, 
reserving the filtrate for the test for arsenic. The precipitate 
on the filter is washed several times with distilled water in 
order to remove all soluble sulphates, and the final residue 
on the filter reserved for the test for lead. 

2, icL) Process for Arsenic. — The filtrate from the insolu- 
ble sulphates, which contains any arsenic that may be 
present, is then introduced into a Marsh apparatus that has 
been previously tested and found to be free from arsenic. 
The approximate quantity of arsenic can be judged from the 
intensity of the mirror of metallic arsenic obtained in the 
delivery tube, and should be expressed in hundredths of a 
milligram. 

Great care should be taken to expel all of the nitric acid 
by means of the sulphuric acid, otherwise an explosion will 
ensue when the solution is put into the Marsh apparatus. 



190 ABNORMAL CONSTITUENTS OF URINE. 

{b) Process for Lead. — The residue on the filter-paper, 
which consists of insoluble sulphates, including lead sul- 
phate, is thoroughly extracted with hot dilute ammonium 
acetate containing an excess of acetic acid, and then filtered. 
A current of sulphuretted hydrogen is passed through the 
filtrate for about an hour, the lead acetate being precipi- 
tated as lead sulphide. Filter, dissolve the residue in hot 
dilute nitric acid, run into an evaporating dish, and evapo- 
rate to dryness over a water-bath. The residue in the dish 
is then dissolved in hot dilute acetic acid and filtered. The 
filtrate, which contains the lead in the form of an acetate, 
is then treated with either a few drops of a saturated solu- 
tion of potassium bichromate, or a few cubic centimeters 
of dilute sulphuric acid, and allowed to stand twenty-four 
hours. The solution that contains the lead chromate or 
sulphate is then filtered, and the precipitate, which is 
usually exceedingly slight, is w^ashed a few times Avith dis- 
tilled w^ater. Sulphuretted-hydrogen water, which has 
been previously filtered, is allowed to pass through the 
filter-paper holding the precipitate, and the filter then care- 
fijlly dried. If lead be present, a slight black precipitate 
will be seen adhering to the surface of the filter-paper near 
its center. 

Mercury. — This substance appears in the urine follow- 
ing the external or internal use of its various compounds. 
The test is applied in the following manner: 

x-\cidulate a portion of the urine with hydrochloric acid, 
then add copper filings, and heat to from 50° to 60° C. for 
about five minutes ; let stand until cool. Wash the copper 
filings, dry, place them in a shallow dish, and at one side 
of the dish, or on a watch-glass that is to be inverted over 
the fihngs, place one drop of a I per cent, solution of gold 
chloride ; heat over a low flame. The mercury that is 
deposited on the copper will be volatilized and will redden 
the solution of gold chloride. According to Brugnatelli,^ 
this test is capable of detecting -^-^ of a milligram of mer- 
cury in one liter of urine. 

Chloral. — A simple test for chloral in the urine is the 
so-called isocyanplicnyl test. The principle of the test de- 

1 " Journ. de Pharm.," April, 1890, p. 367. 



HEMATOPORPHYRIN. 191 

pends upon the fact that an alkah decomposes the chloral 
into formic acid, which immediately unites with the alkali 
to form a formiate and chloroform, which in the presence of 
aniline results in a characteristic volatile compound. 

Test. — Take one-third of a test-tube of urine, and add 
one drop of pure aniline (aniline oil), and about one finger- 
breadth of an alcoholic solution of sodic hydrate, — or an 
equal amount of a strong aqueous solution of sodic hydrate 
and alcohol may be used, — and heat. If chloral be present, 
a volatile compound, having a very disagreeable odor, is 
evolved. 

In many instances this test is very unsatisfactory ; it is, 
therefore, necessary to resort to other more complicated 
methods, the one proposed by Duroy ^ being advised. 

Iodides and Bromides. — Iodides and bromides make 
their appearance in the urine after their administration. The 
presence of iodides is frequently observed in the nitric acid 
test for albumin. Iodine is set free by the nitric acid, and 
appears as a reddish-brown color-zone at the juncture of the 
urine and acid, the color usually becoming gradually diffused 
through the column of acid. When the presence of an iodide 
is suspected, the following test may be readily applied : 

Test. — Take one-half test-tube of urine, add a small 
amount of chloroform, — about one fingerbreadth, — then 
add a few drops of yellow nitric acid, and shake. The 
chloroform takes up the iodine, which is set free by the 
nitric acid, and assumes a pink or purple-red color. 

The presence of bromides is determined in the following 
manner : 

Test. — Proceed exactly as in the test for iodine, care 
being taken to add more of the yellow nitric acid than in 
the test for iodine, in order to completely set free the 
bromine. The chloroform takes up the bromine, and 
assumes an Indian-red color — a mixture of red, yellow, and 
brown. 

HEMATOPORPHYRIN. 

Hematoporphyrin, CjgH^gN203, is a coloring-matter de- 
rived from the blood, and normally present in the urine, 
but only in traces. It was discovered in 1871 by Hoppe- 

1 Wharton and Stille, 1884, p. 395. 



192 



ABNORMAL CONSTITUENTS OF URINE. 



Seyler, who found that by treating hematin with concen- 
trated sulphuric acid and heating, there resulted a com- 
pound whose acid and alkaline solutions showed unusual 
spectral bands. To this new compound he gave the name 
" hematoporphyrin." Since its discovery, it has been recog- 
nized by a number of observers and under a variety of cir- 
cumstances. 

Hematoporphyrin is identical with iron-free hematin 
(Nencki). A urine containing this coloring-matter, when 
viewed by reflected Hght, is opaque and almost black ; or, in 
a thin layer, it is reddish-brown. In an isolated form 



c 
fO zo 



D Eb 

M 60 70 80 sh m 




Fig. 20. — Hematoporphyrin spectra : i, Acid; 2, alkaline; 3, neutral. 



hematoporphyrin is nearly insoluble in water, in dilute 
acetic acid, benzol, and nitrobenzol ; it is slightly solu- 
ble in ether, chloroform, and amyl alcohol, and readily 
soluble in alcohol, alkaline hydrates, and carbonates, as 
well as in dilute mineral acids. 

Spectra. — The acid alcoholic solution shows (Fig. 20, 
i) two absorption bands : one rather dark, situated between 
Frauenhofer's lines C and D, with its right border over- 
lapping D ; and the second, sharply defined, nearly inter- 
mediate between i^ and j5". 

The alkaline solution presents (Fig. 20, 2) a four-banded 



HEMATOPORPHYRIN. 193 

spectrum as follows : A faint and very narrow band about 
midway between C and D ; two between D and E, one 
with its left border near D, the other including E ; the 
fourth band, which is the darkest of all, but which, how- 
ever, is not well defined, includes nearly all of the space 
between b and F, and incloses F. 

The neutral and metallic spectra are represented in the 
accompanying illustration (Fig. 20, 3) ; they are less char- 
acteristic than the acid and alkaline spectra, and therefore 
will not be described here in detail. 

Clinical Significance. — Since urine normally contains 
traces of hematoporphyrin, its presence becomes of im- 
portance only when it is present in large amounts. It was 
first discovered in the urine by Baumstark (1874) in a case 
of leprosy, and then by MacMunn, le Nobel, and others in 
acute articular rheumatism. Neusser found this pigment 
in cases of phthisis pulmonalis, and pleurisy with effusion. 
Perhaps its most frequent appearance in large amounts is fol- 
lowing the prolonged use of sulphonal, trional, or tetronal ; 
it is only rarely found after one or two doses of any one 
of these three drugs. ^ It is commonly found in cases 
of lead-poisoning, of which Nakarai has reported six ; the 
author has met with it in cases of lead-poisoning, but 
never in large quantities. This coloring-matter has also 
been observed in cases of intestinal tuberculosis (Nakarai). 
The bearing of nervous phenomena upon the production 
of hematoporphyrinuria is a subject that requires further 
study. In two cases reported by Rankin and Partington 
and one by the author, obscure nervous symptoms were 
prominent, and possibly had some bearing on the cause of 
the hematoporphyrinuria. 

Separation of Hematoporphyrin. — Salkowski's 
Method. — This method may be employed when the pig- 
ment is present in large quantities. 

''Take about 30 c.c. of urine, add baryta mixture (equal 
parts of a 10 per cent, solution of barium chloride and a 
saturated solution of barium hydrate), until it is completely 
precipitated. Wash once with water, and once with abso- 
lute alcohol, using the latter drop by drop. Transfer the 
precipitate to an evaporating dish, add from 6 to 8 drops 
of concentrated hydrochloric acid and sufficient absolute 

^Ogden, "Boston Medical and Surgical Journal," Feb. 24, 1898. 
13 



194 ABNORMAL CONSTITUENTS OF URINE. 

alcohol to make a thin pap, then stir thoroughly. Heat 
over a water-bath, filter through a dry filter-paper, and 
finally add sufficient absolute alcohol to make from 8 to 
lO c.c. of filtrate." 

Garrod's Method. — This method should be used for 
the detection of small quantities of hematoporphyrin in the 
urine. 

Process. — Precipitate lOO c.c. of the urine with about 
20 c.c. of a 10 per cent, solution of caustic soda. The pre- 
cipitate of phosphates carries down the pigment with it. 
Treat the precipitate with absolute alcohol and hydrochloric 
acid in the manner given above. (See Salkowski's Method.) 

The acid solution obtained by either the Salkowski or the 
Garrod method may be examined directly with the spectro- 
scope for the bands of acid hematoporphyrin, or it miay be 
rendered alkaline, preferably with ammonic hydrate, and 
examined for the characteristic bands of alkaline hemato- 
porphyrin. 

The spectroscopic examination of this alcoholic solution 
must be made within a few hours after its preparation, since 
the solution readily decomposes, after which it is useless 
for observation. 

Detection. — This coloring-matter can only be detected 
with certainty by means of ihe spectroscope. The four 
spectral bands of the alkaline solution are most charac- 
teristic. 



MELANIN. 

Melanin is a pigment that is sometimes found in the 
urine of persons suffering from pigmented tumors. It is 
usually found in solution in the urine, and more rarely in 
the form of small black granules which are in suspension. 
Freshly voided urine containing melanin is usually trans- 
parent and of a normal color. When, however, the urine 
is allowed to stand exposed to the air, the color changes to 
a brown, and finally to a black. Only in rare instances is 
the urine black when it leaves the body. 

Melanin is eliminated in the form of a chromogen, — mela- 
nogen, — which becomes oxidized in the air or by oxidizing 
agents, with a resulting dark or black color due to a de- 
posit of the pigment, melanin. Just where this pigment 
is converted into a chromogen in the body has not yet been 



MELANIN. 195 

determined. Ganghofner and Pribram claim that the change 
takes place in the liver, but this is still a matter of doubt. 

Melanin is insoluble in water, ether, amyl alcohol, and 
dilute acids. It is readily soluble in sodic and ammonic 
hydrates, sodic carbonate, and monosodic phosphate ; hence 
it is not precipitated carbon. It contains iron, sulphur, 
and nitrogen. The chromogen, melanogen, is readily oxi- 
dized by potassium bichromate with sulphuric acid, a five 
per cent, solution of chromic acid, fuming nitric acid, 
potassium permanganate, and potassium chlorate with 
hydrochloric acid, with a resulting black color. 

Litten observed that urine containing melanin did not 
undergo ammoniacal fermentation, but, instead, became 
more acid than normally with the formation of a thick 
fungus-growth on its surface. He also found that the 
urine often contained a reducing substance similar to 
glucose ; such a reaction, however, has not been reported 
by other observ^ers. 

Clinical Significance. — Melanuria is most commonly 
seen in case of melanotic sarcoma in some part of the 
body, not necessarily in the kidneys. It has, very rarely, 
been observed to a marked degree in severe wasting dis- 
eases, and has also been observed in persons suffering from 
repeated attacks of intermittent fever. The urine of indi- 
viduals suffering from melanotic new growths may be en- 
tirely free from melanin while the growth is actively pro- 
gressing. 

Detection. — i. The most sensitive test for the presence 
of melanin is the addition of bromine water, which causes 
a yellow precipitate that gradually blackens (Zeller). 

2. A few drops of a fairly concentrated solution of ferric 
chloride will cause the urine to turn gray : if more be added, a 
precipitate of phosphates falls, carrying the coloring-matter 
with it, and again dissolves with an excess of the iron solu- 
tion (v. Jaksch, Pollak). 

3. Sodium nitroprusside with caustic potash and acetic 
acid gives a deep-blue color, probably due to the formation 
of soluble and insoluble Prussian blue (v. Jaksch). This 
test, however, can not always be obtained with melanin 
that has been isolated from the urine, and the reaction must 
not be regarded as a test for melanin, or only when other 
tests have shown the presence of melanin or melanogen. 

Morner separated the coloring-matter that was in the 



196 ABNORMAL CONSTITUENTS OF URINE. 

form of a chromogen in the urine by precipitating with 
bar\^ta water, and then purifying. 

PTOMAINES AND LEUCOMAINES— TOXICITY OF URINE, 

Ptomaines may be defined as organic chemic com- 
pounds, basic in character, and formed by the action of 
bacteria on nitrogenous matter. On account of their basic 
properties, in which they resemble the vegetable alkaloids, 
ptomaines may be called putrefactive alkaloids. They have 
also been called animal alkaloids, but this is a misnomer, 
because, in the first place, some of them are formed in the 
putrefaction of vegetable matter, and, in the second place, 
the term "animal alkaloids" is more properly restricted 
to the leucomaines, — those basic substances which result 
from tissue metabolism in the body. 

While some of the ptomaines are highly poisonous, this 
is not an essential property, and others are wholly inert. 
Indeed, the greater number of those which have been iso- 
lated up to the present time do not, when employed in single 
doses, produce any apparent harmful effects. Brieger re- 
stricts the term ptomaine to the nonpoisonous basic pro- 
ducts, and designates the poisonous ones as ''toxines." 

Since all putrefaction is due to the action of bacteria, it 
follows that all ptomaines result from the growth of these 
organisms. The kind of ptomaine formed will, therefore, 
depend upon the individual bacterium engaged in its pro- 
duction, the nature of the material being acted upon, and 
the conditions under which the putrefaction goes on, such 
as the temperature, the amount of oxygen present, and the 
duration of the process. 

All ptomaines contain nitrogen as an essential part of 
their basic character. In this they resemble the vegetable 
alkaloids. Some of them contain oxygen, while others do 
not. The latter correspond to the volatile vegetable alka- 
loids, nicotine and coniine, and the former correspond to 
the fixed alkaloids. 

It was formerly supposed that putrefaction was simply 
oxidation, but the researches of Pasteur and others have 
demonstrated the fact that countless myriads of minute 
organisms are engaged constantly in transforming matter 
from organic to the inorganic form. Hermetically seal the 
organic matter and it will remain unchanged indefinitely. 



PTOMAINES. 197 

According to Pouchet, healthy urine contains traces of 
certain toxic substances of an alkaloidal nature ; and accord- 
ing to the researches of Bouchard, Lepine, and Guerin, 
these bodies are more abundant under diseased conditions. 
They were found by A. VilHers as an invariable manifesta- 
tion in measles, diphtheria, and pneumonia. Pouchet found 
in the urine of cholera an alkaloid which was not identical 
with that observed by him in the feces of the same disease. 
Feltz found similar bodies in the urine of cancer patients, 
and Lepine in that of pneumonia. Toxines have been 
found in the urine of scarlet fever and pneumonia (Albu) ; in 
carcinoma of the stomach, and in Addison's disease (Ewald, 
Jacobsen). Bouchard discovered that human urine acted 
as a poison when injected into the veins of a rabbit, and he 
referred the toxic effects to various substances, among which 
were animal alkaloids. 

A. B. Griffiths ^ has pubHshed a series of unnamed alka- 
loids which he has isolated from the urine in the following 
diseases : Parotitis, scarlet fever, diphtheria, measles, per- 
tussis, glanders, pneumonia, epilepsy, erysipelas, puerperal 
fever, eczema, influenza, carcinoma of the uterus, pleuritis, 
and . angina pectoris. 

The experiments of Albu ^ have, in many instances, con- 
firmed those of Griffiths. Albu found alkaloids in the 
urine of cases of scarlet fever, measles, pneumonia, diph- 
theria, phthisis with hectic fever, sepsis accompanying car- 
cinoma of the uterus, erysipelas, Basedow's disease, tetanus, 
pernicious anemia, autointoxication with urticaria following 
acute gastric catarrh, and in diabetic coma. 

Leucomaines are those basic substances which are found 
in the living tissues, either as the products of fermentative 
changes other than those of bacteria, or of retrograde 
metamorphosis. The first attempt at the systematic study 
and generalization of these basic substances was made by 
Gautier, who included under this subject all of those 
substances which are formed in animal tissues during 
normal life, in contradistinction to the ptomaines or basic 
products of putrefaction. The distinction between vege- 

1 " Comptes Rendus," cxiii, 656; loc. cit., cxiv, 497; loc. at., cxv, 185, 
667, 668; loc. cit., cxvi, 1205; loc. cit., cxvii, 744; loc. ciL, cxviii, 1350; 
loc. cit., cxix, 1382; loc. cit., cxx, 1128; "Chem. News," lxx, 199; 
*'Chem. Centralbl.," 1894, 11, 1000. 

2 A. Albu, " Berliner klin. Wochenschr.," xxi, 8 u. 1081, 1894. 



198 ABNORMAL CONSTITUENTS OF URINE. 

table and animal alkaloids is not well defined. Vegetable 
tissues are known to contain not only what are ordinarily 
designated as ptomaines, such as choline, but also leuco- 
maines, such as hypoxanthin, xanthin, etc. Under this head 
must also be placed, on account of their relationship to 
xanthin, those well-defined alkaloidal bases, caffein and 
theobromin. 

The leucomaines proper may be divided into two distinct 
and well-defined groups — (i) the uric acid group, and (2) 
the kreatinin group. 

The first of these groups contains a number of well- 
known bases, w^hich are closely related to uric acid. They 
are as follows : Adenin, hypoxanthin, guanin, xanthin, 
(uric acid), heteroxanthin, methylxanthin, paraxanthin, 
carnin, episarkin, pseudoxanthin, cytosin, gerontin, sper- 
min. 

The members of the kreatinin group have all been dis- 
covered by Gautier, and by him are regarded as allied to 
kreatm and kreatinin. They are as follows : Kreatinin and 
kreatin, crusokreatinin, xanthokreatinin, amphikreatin, and 
two unknown bases. 

Toxicity of Urine. — The question of the toxicity of 
normal urine has been the subject of much controversy. 
From the experiments of Feltz and Ritter, Astaschewsky, 
Schiffer, Bouchard, Lepine, Stadthagen, Gautier, Guinard, 
and others, it can now be positively stated that normal 
urine does possess a certain degree of toxicity. It is more 
difficult to decide upon the nature of this poison. 

Feltz and Ritter, and, independently, Astaschewsky, 
arrived at the opinion that the toxicity was chiefly due to 
the potassium salts of the urine. Although Schiffer ac- 
knowledged the presence and action of the inorganic salts, 
he maintained that the urine contained a definite organic 
poison for the reason that the concentrated aqueous solu- 
tions from alcoholic extracts of the urine-residue killed 
large rabbits in doses corresponding to from i to i ^ liters 
of urine deprived of inorganic salts. 

Bouchard has shown that from 30 to 60 c.c. of normal 
urine, injected mtravejtously, will kill a rabbit w^eighing one 
kilogram. Hence a man weighing 60 kilograms, and ex- 
creting 1200 c.c. per diem, would, if 50 c.c. are necessary 
to kill one kilogram of living matter, secrete enough poison 
to kill 24 kilograms of animal. Bouchard claims that 



TOXICITY OF URINE. 199 

there are five different poisons that may be met with in the 
urine, each one of which produces a definite symptom : 
viz., narcosis, sahvation, mydriasis, paralysis, and convul- 
sions. He found that the day-urine, which is chiefly nar- 
cotic, is from two to four times more toxic than that 
secreted during sleep, and that the latter induces convulsions 
and is antagonistic to the former. Further, that the toxicity 
is independent of the density, since night-urine is denser 
than that secreted during the day. Bouchard also claims 
that the greater part of the toxicity of urine is due to 
organic poisons, especially to coloring-matters ; and that the 
potassium salts are regarded as the cause of only a small 
fraction of the toxicity. 

Lepine also found that about 60 c.c. of urine were suffi- 
cient to kill I kilogram of animal. To the inorganic salts, 
however, he ascribed a much greater importance, inasmuch as 
he estimates that 85 per cent, of the intoxication is due to 
this cause. Stadthagen has also arrived at practically the 
same conclusion, that from 80 to 85 per cent, of the tox- 
icity is due to the inorganic constituents. A part of the 
toxic matter^! 5 to 20 per cent. — is therefore due to organic 
substances. No one organic substance in the urine, such 
as urea, kreatin, kreatinin, etc., possesses this toxicity. 

It is now a well-established fact that the urine of certain 
infectious diseases, such as cholera (Bouchard) and septi- 
cemia (Feltz), is far more poisonous than normal urine. 
That the poisons, basic or otherwise, which are generated 
within the body by the activity of bacteria can be excreted 
in the urine is seen in the fact that immunity to the action 
of bacillus pyocyaneus has been conferred on animals by 
previous injection of urine taken from animals inoculated 
with that bacillus (Bouchard), or with filtered cultures of 
the same (Charrin and Ruffer). 

Furthermore, the excretion of the tetanus and diphtheria 
poisons by the urine has been shown to take place. Thus, 
Brunner demonstrated the tetanus poison in the urine of 
experimental animals, but failed with the urine of the dis- 
ease in man. Bruschettini, however, with the urine of a 
tetanus patient, produced tetanic symptoms in mice by the 
injection of from 3 to 10 c.c. subcutaneously. In the urine 
from diphtheria patients Roux and Yersin demonstrated the 
presence of the diphtheritic poison by inducing paralysis in 
animals. Although basic substances are not present in the 



200 ABNORMAL CONSTITUENTS OF URINE. 

urine of cholera, they are present in the intestinal discharges 
(putrescin in only one of four cases — Roos). From cholera 
feces Pouchet extracted an oily fluid very poisonous to 
frogs ; whereas Villiers obtained a base which produced 
convulsions in guinea-pigs. 

In the consideration of the toxines in the urine of infec- 
tious diseases it must not be forgotten, as pointed out by 
Jawein, that the poison as well as the specific germ may be. 
present in the urine. Thus, in rabbits that died as a result 
of infection with anthrax bacillus, erysipelas streptococcus, 
Eberth's bacillus, and Frankel's diplococcus, the urine 
was found to contain these organisms. 



CHAPTER VI. 

URINARY SEDIMENTS. 

It has already been stated that strictly normal, freshly 
passed urine of acid reaction contains no sediment except 
faint flocculi of mucus, which gradually subside toward 
the bottom, and entangle a few mucus-corpuscles and an 
occasional epithelial cell. Should the urine, however, be 
alkaline, as is frequently the case three or four hours after 
a meal, it may be more or less cloudy at the moment it is 
passed, and quickly deposit a flocculent precipitate of earthy 
phosphates, which may occupy considerable bulk. Upon 
microscopic examination the sediment will be found to con- 
sist of amorphous granules, which will quickly disappear on 
the addition of a few drops of acetic acid. 

When a normal urine without sediment has stood for 
some time, especially at a moderate or low temperature, 
there is frequently observed a deposit of amorphous gran- 
ular matter, usually of a pink color, and sometimes it is 
almost colorless. It is readily soluble by heat, and is 
composed of amorphous urates — a mixture in varying pro- 
portions of acid urates of potassium, sodium, and ammo- 
nium, with which urates of calcium and magnesium are 
occasionally commingled. Such a deposit of urates may 
also contain crystals of uric acid or octahedral crystals of 
calcium oxalate. Bacteria from the air and other sources 
frequently make their appearance in the sediment ; also, 
often, spores of torula cerevisiae — the yeast fungus — and 
spores of penicillium glaucum are found. 

When a urine becomes alkaline as a result of the de- 
composition of the urea into ammonium carbonate, it has 
an entirely different appearance, and it is at this time that 
we find myriads of bacteria, together with a deposit of 
phosphates, both amorphous and crystalline. At the very 
beginning of the reaction, when the urine may still be 

201 



202 URINARY SEDIMENTS. 

neutral or even faintly alkaline, any crystals of uric acid that 
may be present begin to dissolve and to change their form 
so as to become more or less unrecognizable, while on their 
fragments may often be seen to adhere prismatic crystals of 
urate of sodium and dark spheres of urate of ammonium. 
As the reaction becomes more strongly alkaline the uric 
acid disappears altogether, and the field becomes crowded 
with granules of amorphous phosphate of lime, beautiful 
triangular prisms ('' coffin-lid " shaped crystals) and irregu- 
larly shaped crystals of ammonio-magnesium phosphate, 
and the dark spheres of urate of ammonium which are often 
beset with spiculae. (Fig. 28.) 

The methods used for the examination of urinary sedi- 
ments are both microscopic and chemic. By means of the 
microscope various deposits are recognized by characteris- 
tics that are in themselves diagnostic. But the micro- 
scope does not in all instances reveal the exact nature of 
certain substances, and then it becomes necessary to resort 
to chemic tests, which, together with the microscope, afford 
reliable data concerning the substances examined. 

METHODS OF OBTAINING URINARY SEDIMENTS. 

Two methods are in common use for obtaining urinary 
sediments — /. e., (^) cejitriftLgal method and {b) gravity 
inetliod. 

(a) Centrifugal Method. — More recent experience has 
demonstrated the immense advantages of the centrifugal 
method of obtaining urinary sediments for purposes of 
microscopic examination. The principle of this method de- 
pends upon the fact that when the urine is placed in tubes 
and revolved at a high speed upon horizontal rotating arms, 
a centrifugal force is exerted upon all solid particles in the 
urine, hundreds of times greater than gravity, and, conse- 
quently, the urinary sediment is deposited in the bottom of 
the tubes almost immediately, irrespective of the specific 
gravity of the urine or the character of the sediment. 
Some of the advantages of this method are as follows : 

1. Centrifugal sedimentation of the urine permits of an 
immediate microscopic examination, instead of waiting for 
from twelve to twenty-four hours as by the old method of 
gravity. 

2. The centrifugal method secures more completely con- 



CENTRIFUGAL METHOD. 



203 



centrated sedimentation, and, therefore, it is better suited 
for purposes of microscopic diagnosis. 

3. Microscopic examination of freshly voided urine may 
be made before casts or morphologic elements have had 
time to undergo maceration or solution in the urine, and 
before the appearance of large numbers of bacteria, which 
always greatly obscure the microscopic field. 

4. It affords the only positive means of distinguishing 
between primary and secondmy crystalline elements in 
the urine, since by this method only can the urine be 




Fig. 21. — The Purdy electric centrifuge. 



examined microscopically as soon as voided, and, there- 
fore, before the formation of those crystals that are de- 
posited in nearly all normal urines that are left standing 
for several hours. 

5. By the old method of gravity, it sometimes happens 
with urines of high specific gravity that the lighter casts 
(such as those of the narrow, hyaline order) fail to settle, 
and thus elude detection. The centrifuge precipitates all 
casts without delay, irrespective of the above-named condi- 
tions. 



204 



URINARY SEDIMENTS. 



It will, therefore, be readily seen that the centrifuge is 
destined to supersede the old method of gravitation for all 
purposes of urinary sedimentation. 

Of the various number of centrifugal machines on the 
market the electric centrifuge devised by Dr. Purdy, of 
Chicago, is undoubtedly the most serviceable. 

The Piirdy electric centrifuge,'^ shown in figure 21, can 
be operated on the interrupted incandescent illuminating 
current, on the constant illuminating current, on the storage 



C.C 



I -J- 



j:-^ 





Fig. 22. — Tubes for the Purdy centrifuge : c, Percentage tube ; b, sediment tube. 



current, and on the galvanic current (sulphuric cell) ; and 
is suitably adjusted for operation at any voltage from 10 to 
120 volts, providing the nature and strength of the current 
be specified. 

The apparatus is capable of all grades of speed from 500 
to 10,000 revolutions per minute, according to the strength 
of the current used and the resistance of the arm. When 
the sediment tubes (Fig. 22), each with a capacity of 15 

1 The Purdy electric centrifuge is manufactured by Williams, Brown and 
Earle, 918 Chestnut St., Philadelphia. 



CENTRIFUGAL METHOD. 



205 



c.c, are filled and introduced into the aluminium shields of 
the apparatus, it is capable of sustaining a speed of from 
2000 to 2500 revolutions per minute, the tips of the tubes 
at the same time describing a circle, the diameter of which 
is 1 3 ^ inches. The centrifugal force is from two to three 
thousand times greater than gravity, so that all the elements 
of a sediment — organized and nonorganized — are in from 
three to five minutes forced to the extreme tips of the tubes, 
where they may at once be utiHzed for microscopic purposes. 
Concerning the Jiand centrifuge, of which there are a large 




m 



Fig. 



23.— The Bausch and Lomb spiral-gear urinary centrifuge with tubes (one-fourth 
actual size). 



number on the market, it is to be said that only a compara- 
tively few are of practical value. The spiral-gear centri- 
fuge, manufactured by The Bausch & Lomb Optical Co., 
of Rochester, N. Y., has been extensively used by the 
author, and can be highly recommended. 

The centrifuge proper (Fig. 23) consists of a small circu- 
lar case containing a train of gears made of extra hardened 
bronze, and having teeth spirally cut, three of which are 
engaged at all times. This form of gearing runs easier and 



206 



URINARY SEDIMENTS. 



is more durable than any of the straight gear machines, as 
it prevents backlash or lost motion. The centrifuge is very 
small, yet it is strong and capable of a high rate of speed — 
3000 revolutions per minute. 

The glass tubes used for holding the urine are both gradu- 
ated and plain, and have practically the same shape as 
those already described in connection Avith the electric 
centrifuge. These tubes are car- 
ried in aluminium shields, and are 
supported on elastic cushions to 
prevent breakage during rotation. 
(b) Gravity Method.— The old 
so-called gravity method of obtain- 
ing a sediment, and one that is not 
without advantages at the present 
time, consists in placing the urine 
in a urine glass (Fig. 24) having 
parallel sides and a concave bot- 
tom, ^ then covering with a piece of 
filter-paper, a glass plate, or other 
convenient article, in order to keep 
out dust and other foreign matter. 
Allow the glass to stand, prefer- 
ably in a dark and moderately cool 
place, until the urine is well settled. 
The time required for a sediment 
that is suitable for microscopic ex- 
amination is from one to twenty- 
four hours ; usually a satisfactory 
sedim^ent is obtained within twelve 
hours. Occasionally, in a normal 
urine or one of high specific grav- 
ity, the sediment does not fall to 
the bottom of the glass, but, instead, is suspended in the 
column of urine ; this cloud is sometimes termed the 
"nubecula." 

The chief objection to the use of this method is the 
length of time required for the urine to settle. Further- 




Fig-. 24. — Urine or sediment 
glass. 



^ The urine glass, also sometimes termed sediment glass, should be made 
of perfectly clear, smooth glass which is free from air-bubbles. The bottom 
of the glass should be concave and without the objectionable upward, nipple- 
like projection so often found in the ordinary sediment glass. These glasses 
can be obtained of Richard Briggs Co., 287 Washington Street, Boston. 



GRAVITY METHOD. 



207 



more, unless preservatives are used, the urine often un- 
dergoes alkaline decomposition before a sediment settles, 
when it becomes unfit for microscopic examination. But 
preservatives may be used without altering the sediment or 
otherwise interfering with the microscopic examination. 
Whenever this method is used, it is the habit of the writer 
to add to that portion of the urine that is set aside for 
sediment from 15 to 30 c.c. of a saturated 
{4 per cent.) solution of boric acid, which, 
under ordinary conditions, preserves the 
urine until the sediment is satisfactorily 
settled. A drop or two oi forniahn (for- 
maldehyde gas in water) may be added to 
the urine, but not always with satisfactory 
results, since a peculiar crystalline (?) pre- 
cipitate is often deposited, especially if too 
much is added, which seriously interferes 
with the examination of the sediment. 
Other preservatives, such as chloral, sali- 
cylic acid, chloroform, etc., may be used, 
but with even less satisfactory results. 

There can be no question of the many 
advantages of the centrifugal method over 
the gravity method for obtaining sediments, 
and the writer strongly recommends its use 
for both the practitioner and the student. 
There are, however, two disadvantages : 
viz., (i) by the use of the centrifuge the 
proportion of abnormal elements, such as 
casts, blood globules, pus-corpuscles, etc., 
may be very large, since the greater part ot 
the sediment is included in a drop or two 
of fluid, whereas the sediment obtained by 
gravity might really contain very few ab- 
normal elements ; the examiner is thereby 
misled as to the extent of the pathologic 
process. This is particularly the case in judging of the 
amount of pus which a given urine contains, also the pro- 
portion of crystalline elements in a urine. (2) The drop or 
two of sediment obtained by the use of the centrifuge may 
contain so much pus, so many crystals, or epithelial cells 
as to obscure any renal casts that would otherwise be 
readily detected in a sediment obtained by gravity. 



Fig. 25. — Pipette for 
sediments. 



208 URINARY SEDIMENTS. 



THE PREPARATION OF SEDIMENTS FOR MICROSCOPIC 

EXAMINATION. 

Having obtained a well-settled sediment, either by the 
use of the centrifuge or by allowing the urine to stand in a 
urine glass to settle by gravity, the examiner should supply 
himself with a suitable pipette, slides, and cover-glasses, 
and a microscope of the best make. 

1. Pipette. — Great care should be used in making a 
pipette, for unless the drawn-out tip is of the proper shape 
and the opening of the proper size, a suitable sediment can 
not be obtained. The pipette shown in figure 25 repre- 
sents the approximate size of the glass tubing that should 
be used, and the shape of the drawn-out, or, what may be 
termed the proximal, end. If the proximal tip be abruptly 
drawn to nearly a point, and the opening be too small, a 
good sediment can not be obtained. The other end, or 
distal end, of the glass tube should be rounded off in the 
flame so as to prevent cutting the finger, and the opening 
should be nearly as large as the diameter of the tubing. 

2. Slides and Cover-glasses. — These should be free 
from scratches and h^ perfectly clean. The No. 2 square or 
oval cover-glass is perhaps best suited for the examination 
of urinary sediments. 

3. Microscope. — It will not be necessary here to give a 
detailed description of the microscope or to refer to its use. 
The instrument should be one of the best : viz., the Leitz 
or Zeiss microscope made in Germany, or the Bausch & 
Lomb microscope made by the Bausch & Lomb Optical 
Co., of Rochester, N. Y. For the examination of urinary 
sediments the Abbe condenser can not be satisfactorily 
used, since too much light is furnished thereby, the ordinary 
diaphragm supplied with each instrument being most ser- 
viceable. 

Method. — The pipette, held between the thumb and 
middle and ring-fingers, is carried to the bottom of the 
sediment glass with the index-finger (which should be per- 
fectly dry) pressed upon the distal end. When the pipette 
has reached the heaviest portion of the sediment, it is gently 
rotated between the thumb and fingers without removing 
the index-finger from the distal end, and a small amount of 
the sediment allowed to enter slowly. The pipette is with- 
drawn from the urine and carefully wiped from end to end 



CLASSIFICATION OF SEDIMENTS. 209 

to remove all fluid from its outer surface. Two or three 
slides are then placed on the table, and a drop of the sedi- 
ment placed on each and covered with the cover-glasses. 
The preparations are then ready for microscopic examina- 
tion. The writer, who uses a Leitz microscope, is in the 
habit of examining the specimen first with a low power, — 
No. 5 objective and No. i eye-piece, — and then with a 
higher power — 7 objective and i or 3 eye -piece. Having 
carefully searched the three preparations, it is probable that 
most or all of the elements have been seen. 

It is sometimes necessary, especially if the sediment is 
bulky, to first take a sediment from the upper layer, and 
then one from the bottom layer, in order to be able to 
detect the lighter elements (casts, etc.) and the heavier sub- 
stances (crystals). 

It sometimes happens that casts and cells do not settle, 
but are held in suspension in a cloud near the top of the col- 
umn of urine. When such a cloud is present, a drop of 
sediment from it should always be examined. 



URINARY SEDIMENTS. 

The urinary sediments are best classified, for the purpose 
of study, into two groups — i. e., nonorganized or chemic, 
and organized or anatomic deposits, as follows : 

I. NONORGANIZED. 



I. 


Uric acid 


(crystalline). 


2. 


Urates 


(amorphous or crystalline). 


3. 


Hippuric acid 


(crystalline). 


4. 


Calcium oxalate 


(crystalline). 


5- 


Calcium phosphate 


(amorphous or crystalline). 


6. 


Ammonio-magnesium phosphate — triple phosphate 






(crystalline or amorphous). 


7. 


Calcium carbonate 


(crystalline or amorphous). 


8. 


Cystin 


(crystalline). 


9- 


Cholesterin 


(crystalline). 


10. 


Leucin 


(crystalline). 


1 1. 


Tyrosin 


(crystalline). 


12. 


Hematoidin — bilirubin (crystalline). 


13. 


Xanthin 


(crystalline or amorphous). 


14. 


Indigo 
14 


(crystalline). 



210 URINARY SEDIMENTS. 

II. ORGANIZED. 

1. Epithelium. 

2. Nucleo-albumin (mucin). 

3. Blood. 

4. Pus. 

5. Renal casts. 

6. Spermatozoa. 

7. Fat. 

8. Fibrin. 

9. Fungi and infusoria. 

10. Morbid growths. 

11. Parasites. 

III. EXTRANEOUS SUBSTANCES. 



NONORGANIZED SEDIMENTS* 

The nonorganized or chemic sediments of the urine are 
usually crystalline, although in a few instances they are 
amorphous, and are to be distinguished from the organized 
sediments described under a separate heading. 

Uric Acid.^ — Uric acid crystals are frequently found as 
constituents of the urinary sediment. They always occur 
in an acid urine, and usually in one that is strongly acid. 
They appear in normal as well as in pathologic urine. The 
crystals are usually colored a deep yellow or orange -red, 
sometimes a pale yellow, and sometimes brown, and occa- 
sionally they are colorless. Pii7'e uric acid is very difficultly 
crystallizable ; therefore, the crystals of uric acid found in 
the sediment are those of the impure acid. 

Uric acid crystallizes in a variety of shapes, but the 
typical shape may be said to be the rhombic plate. It is, 
however, comparatively rare to find these typical forms in 
the sediment, the great majority of the crystals found being 
modifications of this form. (Fig. 26.) Thus we find the 
rectangular prisms, the barrel, whetstone, club, spear, 
wedge, dumb-bell, and diamond shapes ; also the crystal 
resembling a comb with teeth on two sides, the rosette 
(coalescence of crystals of varying shapes) and irregularly 
shaped crystals, all of which have a more or less yellow 
color, except the diamond form, which is not infrequently 

1 For General Consideration, Properties, and Tests for Uric Acid see pages 
59 to 72. 



URIC ACID. 



211 



nearly colorless. There are many more forms of uric acid 
cr}^stals than those mentioned, and practice soon teaches 
one to recognize these varied forms, even though they may 
deviate much from the typical shape. The rosette form 
(Plate 5) may at times be fan shaped ; and, again, the indi- 
vidual ciystals may have coalesced so as to form a large, 
solid, compact spherule, often with sharp spicules projecting. 
These large rosettes and spherules of uric acid frequently 
have the appearance of particles of sand, hence the term 
uric acid sand. Occasionally, the coalescence of the uric 




Fig. 26. — Forms of uric acid : i, Rhombic plates ; 2, whetstone forms ; 3, 3, quadrate 
forms ; 4, 5, prolonged into points ; 6, 8, rosettes ; 7, pointed bundles ; 9, barrel forms 
precipitated by adding hydrochloric acid to urine. 



acid crystals results in much larger bodies, which have been 
termed tiric acid gravel, and still larger, tunc acid calcidi. 
Ultzmann claims that the irregular forms of uric acid, espe- 
cially the rough and pointed forms, are almost always an 
accompaniment of uric acid calculi. 

Uric acid crystals may be either primary (those separating 
from the urine inside the body) or secondary (those separating 
from the urine outside the body), but the author knows of 
no certain means from the appearance of the crystals them- 
selves of distinguishing between the two. The only certain 



212 URINARY SEDIMENTS. 

means of determining the presence of the primary crystals 
is to obtain a freshly passed specimen and, after thoroughly 
agitating, centrifugalize while still warm — it may be neces- 
sary to centrifugalize several portions in order to obtain the 
crystals, if present. With these precautions, any crystals 
found are primary ; such crystals are usually highly col- 
ored, compact, and in the form of the rosette or spiculated 
spherule, although other forms may be primary. 

All acid urines tend to deposit their uric acid sooner or 
later. The time of onset of precipitation varies from a 
few hours to five or six days, or even longer. It possesses 
a strong tendency to crystallize upon contact with any 
organic or inorganic substances ; thus, upon standing the 
crystals often cling to the sides of the glass or to threads 
or specks suspended in the urine. This fact renders it 
more liable than any other crystalline deposit to form about 





/ 




Fig. 27.— Acid sodium urate cr>'stals. 

a nucleus in the urinary tract and result in gravel or cal- 
culi. 

Urates. — (a) Acid Sodium Urate. — This salt of uric 
acid occurs in urine of acid, neutral, or faintly alkaline reac- 
tion, and is generally amorphous, but sometimes crystalline. 
When amorphous, it forms a predominant part of the de- 
posit of amorphous or mixed urates, seen in the bottom of the 
vessel after the urine cools. It crystallizes in colorless, 
prismatic, needle-like crystals, which are usually arranged in 
stellate (star-like) clusters. (Fig. 27.) Occasionally, the 
needle crystals are found alone. Sometimes the clusters 
have a dumb-bell appearance, each half of which is striated 
and broad at the extremities ; one-half of one of the 
dumb-bell-like clusters, viewed from above, would be fan 
shaped. 

Acid sodium urate is very insoluble in cold water (1200 
parts) but quite soluble in hot water. 



Plate 5 




Uric- ACID Crystals with Amorphous Urates (after Peyer), 



URIC ACID AND URATES. 



213 



(b) Acid Ammonium Urate. — This is crystalline and 
occurs in the urinary sediment as yellowish-red or dark- 
brown spherules, which are studded with fine, sharp-pointed 
spicules. To these the terms ** thorn-apple crystals " and 
"hedge-hog crystals" have been given. These spicules 
may be short or long, sometimes branched, curved, or 
bent. (See Plate 6.) It also frequently crystallizes in 
fine needles, which are in clumps, having a sheaf-of-wheat 
arrangement ; and sometimes in the center of a clump a 
small spherule may be found embedded. These crystals 
are also colored dark-brown, and should not be mistaken 
for tyrosin crystals or the groups of colorless crystals of 



- c 




Fig. 28. — Deposits in ammoniacal urine (alkaline fermentation) : A, Acid ammonium 
urate ; B, bacterium ureae ; C, ammonio-magnesium phosphate. 



acid sodium urate, although by some they are considered 
identical with the latter. 

The crystals of acid ammonium urate are soluble in hot 
water, and dissolve in hydrochloric acid and other acids, 
with the subsequent precipitation of uric acid crystals. 
When they are treated with potassic hydrate, the odor of 
ammonium is evolved. 

The crystals often occur in acid urine with a deposit of 
amorphous urates. They are very frequently deposited 
during the alkaline fermentation of the urine, and are found, 
along with amorphous earthy phosphates and crystals of 
ammonio-magnesium phosphate. (Fig. 28.) It is, in fact, 
the only urate found in strongly alkaline urine. 



214 URINARY SEDIMENTS. 

(c) Acid Potassium Urate. — This exists in acid urine, 
is amorphous, and forms a part of a deposit of amorphous 
urates. Like acid sodium urate, it is very insoluble in cold 
and quite soluble in hot water. 

(d) Acid calcium urate is a constituent of acid urine, 
but occurs only rarely and usually in small quantity in a 
deposit of amorphous urates. It is an amorphous white 
powder, difficultly soluble in cold water, faintly soluble in 
hot water, and is known to have calcium for its base, since, 
upon incineration, it leaves a residue of calcium carbonate. 

Amorphous or Mixed Urates. — These consist, as 
mentioned, of acid sodium urate, acid potassium urate, 
ammonium urate, and sometimes acid calcium and mag- 
nesium urates. A deposit of amorphous urates frequently 
occurs in urine, more especially in concentrated urine, 
upon cooling to the room-temperature, and particularly if 
subjected to a low temperature. The deposit usually 
falls rapidly to the bottom of the urine glass, and when 
settled, has a pink or yellowish-red color due to uroery- 
thrin ; it may rarely be colorless. Occasionally, a portion 
of the deposit is so finely divided that it will not settle, the 
urine remaining turbid throughout ; but even under such 
circumstances the greater part settles, forming a heavy 
deposit. 

Detection of Amorphous Urates. — First determine the 
reaction of the urine, and if acid, pour a small portion of 
the turbid urine into a test-tube and heat gently, but avoid 
the boiling temperature. If amorphous urates are present, 
they are dissolved by the heat, and the urine becomes clear. 
They are dissolved by an alkaline hydrate, but with the 
simultaneous precipitation of the earthy phosphates. When 
amorphous urates are treated with acetic acid or any of the 
strong mineral acids, they are dissolved, with the subse- 
quent crystallization of uric acid. They also respond to 
the murexide test. 

Treatment of a Sediment Containing Amorphous 
Urates. — It is obvious that when a sediment consists chiefly 
of amorphous urates, most of the formed elements will be 
obscured by the abundance of urate granules ; it, therefore, 
becomes necessary to get rid of the amorphous urates be- 
fore a satisfactory microscopic examination can be made. 
This is best accomplished in the following manner : 

Fill a urine glass with the urine, allow the sediment to 



Plate 6 




Ammonium Urate, showing Spherules and Thorn-apple-shaped 
Crystals (after Peyer). 



URIC ACID AND URATES. 215 

settle thoroughly ; decant the supernatant urine, and then 
add warm water to the sediment, using an amount of water 
equal to the quantity of urine originally taken. The warm 
water dissolves the urates and, at the same time, dilutes the 
urine so that they will not reform. Then allow the sedi- 
ment to settle again, or centrifugalize, and examine in the 
usual way. 

Aside from the solution of the urates, the addition of 
warm water modifies the sediment in only one particular — 
/. e., any normal blood present will become swollen and lose 
its color (abnormal blood). 

Care should be taken to avoid the use of boiling water, 
or water having a high temperature, else any albumin 
present will be coagulated, rendering the sediment unfit 
for examination. 

Clinical Significance. — /. Uric Acid : Uric acid crys- 
tals are frequently found in the urine of persons who are in 
perfect health, especially when the urine is concentrated or 
unusually acid. As has been mentioned, a deposit of uric 
acid crystals does not necessarily indicate an increase of uric 
acid in the urine, for, as a matter of fact, a deposit may 
occur even when the uric acid is much diminished. Any 
urine upon standing for several hours is apt to deposit 
crystals of uric acid. Under such circumstances crystals of 
uric acid are of no clinical importance. 

A deposit of uric acid is often the result of a hearty meat 
diet, especially when coupled with sedentary habits of life 
and faulty digestion. Likewise, a deposit is frequently a 
result of increased tissue metabolism and, consequently, an 
increased formation of uric acid, attended with emaciation^ 
headaches, and nervous debility. An increased formation 
of uric acid is sometimes the result of conditions in which 
the oxidizing power of the system is seriously impaired, as 
in diseases of the respiratory tract and circulatory organs. 

Uric acid sediments are often met with in acute febrile 
conditions, in which there is a marked diminution in the 
aqueous element and an increased acidity. A deposit of 
uric acid is of frequent occurrence in gout, especially fol- 
lowing a paroxysm ; also in the early stages of chronic 
interstitial nephritis, particularly when the disease is the 
result of gout. Given, then, a patient with gouty ten- 
dencies, who has habitually taken a hearty meat diet, and 
whose urine shows a constant deposit of uric acid crystals 



216 URINARY SEDIMENTS. 

and evidences of more or less renal disturbance, an early- 
stage of chronic interstitial nephritis should be strongly 
suspected. Cry^stals of uric acid are frequently seen tem- 
porarily in the sediment during the convalescent stage of 
an acute diffuse nephritis. 

In the urine of children who are convalescing from scarlet 
fever or other acute exanthem, uric acid deposits are very 
apt to occur, and even uric acid gravel may be found under 
such circumstances. 

Primary uric acid, or that formed inside the body, is 
always of importance. It is frequently accompanied by 
evidences of marked irritation of the kidney or other por- 
tion of the urinary tract. The primary crystals should in 
all instances be distinguished from those that are secondarily 
formed. (Seep. 211.) 

2. Urates : A deposit of amorphous urates, like uric acid, 
often occurs in any urine that is concentrated or unusually 
acid, seen especially in acute febrile diseases. In diseases 
of the liver and heart, also in subacute glomerular (paren- 
chymatous) nephritis, a deposit of amorphous urates often 
takes place. A primary deposit of acid ammonium urate 
is of frequent occurrence in the kidneys of the new-born, 
and crystals of the same may be found in the urine. 
Further than this, the clinical importance of urates is much 
the same as that of uric acid. It should be borne in mind 
that urines that are allowed to stand in a cold place are very 
apt to deposit amorphous urates. 

Phosphates. — The earthy pJiosphates are the only salts 
of phosphoric acid that appear in the urinary sediment. 
They consist of (a) ainnionio-inagnesitun pJwspJiate or triple 
phospliate, and (U) calcium phosphate. These deposits are 
found only in very feebly acid, neutral, or alkaline urine, and 
are most abundant following the alkaline fermentation. 
They appear to the naked eye as bulky, opaque, white de- 
posits, unless they are accompanied by blood, with which 
they are then more or less tinged. The urine itself is likely 
to be turbid from the presence of amorphous phosphate of 
calcium in suspension, especially after a vegetable diet. It 
often has an ammoniacal and sometimes a fetid odor, though 
not necessarily. Phosphatic deposits are especially abun- 
dant in the urine of some affections of the bladder, and often 
attend diseases of the spinal cord, because of paralysis of 
the bladder and consequent retention of urine. 



PHOSPHATES. 



21: 



(a) Ammonio-magnesium phosphate, MgNH^PO^ .- 
6H2O, or triple phosphate, is a crystaUine deposit occurring 
in two forms : 

1. The triangular prism with beveled edges is most 
typical and frequent. (Fig. 29.) There are many modifi- 
cations of this type, one of the most common being the so- 
called *' coffin-lid " crystal, which is the triangular prism with 
one of the three angles wanting. Frequently, the crystals 
are shortened so as to form squares, and these are the ones 
already referred to as being possibly mistaken for the octa- 
hedral crystals of calcium oxalate. 

2. The stellate or feathery crystals of triple phosphate 
(Fig. 29) are less commonly seen. They predominate in 





Fig. 29. — Triple-phosphate crystals. 

the precipitate that follows the addition to the urine of 
ammonic hydrate. These crystals gradually undergo con- 
version into the prismatic form. 

(b) Calcium phosphate is either amorphous (normal 
salt, Ca3(POj2) or crystalline (acid salt, CaHPOJ. (i) 
The amorphous form is most frequently found as a whitish 
flocculent deposit ^ in the after-meal urine. It is often 
precipitated from the urine by heat, and constitutes an 
important source of error in testing for albumin by heat ; 
this precipitate is readily dissolved by acetic acid. This 
form of calcium phosphate sometimes occurs in a very 
feebly acid urine as minute, pale, highly refractive granules, 



1 This deposit usually consists partly of magnesium phosphate. 



218 URINARY SEDIMENTS. 

which are arranged in irregular clumps, and often adherent 
to renal casts or other organized elements of the sediment. 
Amorphous phosphate of lime is a frequent accompaniment 
of triple phosphate in a neutral or alkaline urine. 

(2) Acid calcium phospJiate, or the crystalline form, is fre- 
quently found in urinary deposits, and is often mistaken for 
the crystals of acid urate of sodium. Crystals of acid 
phosphate of calcium sometimes occur alone, sometimes with 
crystals of triple phosphate, and not infrequently with the 
amorphous form of calcium phosphate. They are also met 
with in a urine of weak acid reaction, but one that is about 
to undergo the alkaline fermentation. Acid calcium phos- 
phate crystallizes in the form of prisms that are found either 
singly or in stellate groups. (Fig. 30.) Frequently, the 
groups have a fan-like, and sometimes a club-like, arrange- 




Fig. 30.— Acid calcium phosphate crystals, 

ment. Usually, the individual crystals are small, but may 
be large and thick, with one end beveled to a sharp point, 
with cutting-edges on each side. 

It is often impossible to decide from the microscopic 
appearance of these crystals whether they are acid calcium 
phosphate or acid sodium urate, especially when found in 
a faintly acid urine. These two forms of crystals are dis- 
tinguished by treating them with acetic acid, which rapidly 
dissolves the phosphate crystal, while that of acid sodium 
urate is more slowly dissolved, and is subsequently replaced 
by crystals of uric acid. The crystals of acid calcium phos- 
phate are often accompanied by crystals of calcium oxalate. 

Clinical Significance. — It has already been shown (p. 
29) that a deposit of amorphous phosphates may occur in 
health in a urine alkaline from fixed alkalies, notably two 
or three hours after a hearty meal. If this deposit be tem- 



CALCIUM OXALATE. 219 

porary, it is of no clinical importance ; if, however, it be 
permanent, and the twenty-four-hour urine contain a heavy 
deposit of amorphous phosphates, it becomes of pathologic 
importance, and in most instances indicates a low general 
metabolism. Ordinary tonic treatment usually results in a 
complete disappearance of the deposit. 

■ Crystalline phosphates when deposited zvitJdn the body, 
often cause much damage to the urinary tract. Such de- 
posits consist chiefly of crystals of ammonio-magnesium 
phosphate formed as the result of the presence of a vola- 
tile alkali — ammonia which arises from the decomposition 
of the urea in the urinary passages. This is most com- 
monly encountered in cases of chronic cystitis, chronic pye- 
litis, and pyelocystitis, in which the clinical symptoms are 
mostly irritant in character. The mechanical irritation by the 
cr>^stals, phis the irritating effect of the ammonia, adds much 
to the distress of the patient. The most frequent causes of 
this condition of the urine are obstructive diseases of the 
lower urinary tract. Likewise, those diseases that affect 
the contractile power of the muscles of the bladder. Thus, 
in enlarged prostate, diseases of the spinal cord, paraplegia, 
etc., the urine is retained, and soon undergoes ammoniacal 
fermentation with a resulting deposit of triple phosphate. 
This condition of the urine nearly always precedes the so- 
called ''surgical kidney" and other dangerous septic con- 
ditions that also often result from the introduction of un- 
clean instruments into the bladder. 

Calcium Oxalate.^ — Crystals of oxalate of calcium are 
found in either acid or alkaline urine, but most commonly 
in acid urine ; they are frequently associated with crystals of 
uric acid. When present in an alkaline urine, they are 
usually found along with crystals of ammonio-magnesium 
phosphate, for which they are frequently mistaken. 

When crystals of calcium oxalate are constantly present 
in the urine, the condition is termed oxaluria. 

Calcium oxalate crystallizes in two typical forms — the 
octahedral and dumb-bell crystals. There are, however, 
various modifications of these two forms, according to the 
positions of the crystals. (Fig. 31.) 

I. The octahedral crystals are made up of two four- 
sided pyramids, placed base to base, and when viewed from 

1 For the properties of Calcium Oxalate see p. 97 



220 URINARY SEDIMENTS. 

the side, their characteristic appearance is that of a square 
crossed obhquely by two bright Hnes, forming the so-called 
*• envelop " crystal. If, however, the octahedron be turned 
with one of its long axes toward the observer while the 
other is held upright, the short axis will necessarily be 
transverse, and the crystal will appear as a long and very 
acute octahedron. 

Frequently, the octahedra coalesce in such a way as to 
have the appearance of an open umbrella, constituting the 
so-called ''umbrella" crystals. Sometimes each half of 
an octahedron is connected by a short quadrilateral prism, 
and such have been called " prismatic " crystals of calcium 
oxalate. A few other irregular forms are occasionally 
found, but most of them, if not all, are modifications of the 
typical octahedron. Occasionally, a number of the octa- 



O ^ 

Fig. 31. — Various forms of calcium oxalate crystals. 



hedral crystals are found intimately adherent, forming 
larger or smaller microscopic concretions. Isolated crystals 
are not infrequently found adherent to renal casts. 

2. The dumb-bell and oval crystals of calcium oxalate 
are more rarely found in the urinary sediment than the 
octahedral forms, but when thus met with, are highly char- 
acteristic. The dumb-bell crystals are always associated 
with a larger or smaller number of oval or circular forms, 
which have bright centers showing their biconcavity. In 
addition to these are found allied forms, especially those 
with partial concavities at the sides. Frequently, two dumb- 
bells are found crossed at their centers, forming a double 
dumb-bell crystal. These colorless dumb-bell crystals of 
calcium oxalate should not be mistaken for the yellowish-red 



CALCIUM OXALATE. 221 

or brown dumb-bells of uric acid and of ammonium urate. 
The dumb-bells of uric acid and of ammonium urate are 
readily soluble in alkaline hydrates, while those of calcium 
oxalate are difficultly soluble ; the dumb-bells of uric acid 
are insoluble in dilute hydrochloric acid, while those of 
calcium oxalate are soluble. The dumb-bell or oval crys- 
tals of calcium oxalate are, like the octahedral forms, quite 
often found adherent to renal casts, and a number of them 
may be joined together to form microscopic concretions. 

The small circular ciystals are sometimes mistaken for 
normal blood globules. They are readily distinguished by 
the fact that the oxalate, although biconcave, is very highly 
refractive, colorless, and insoluble in acetic acid, whereas 
the normal blood globule has a pale-yellow color, and is 
rendered abnormal by acetic acid. 

Primary and Secondary Crystals of Calcium Oxalate. 
— T\\Q primary crystals, or those formed inside the body, 
are generally the large octahedra, and also most of the oval 
and ditmb-bell forms. Secondary crystals, or those formed 
after the urine has been passed, are usually the small 
octahedra and perhaps some of the very small oval, circidar^ 
and dumb-bell forms. These secondary crystals are most 
commonly found in a urine that has been allowed to stand 
for some time, when they are frequently accompanied by 
uric acid. Only rarely are the large crystals deposited 
secondarily ; they may, however, be deposited following the 
addition of acetic acid to the urine. 

Distinction Between Crystals of Calcium Oxalate and 
Those of Ammonio -magnesium Phosphate. — The fact that, at 
times, some of the crystals of ammonio-magnesium phos- 
phate (triple phosphate) closely resemble the octahedral 
form of calcium oxalate often leads to much confusion. 
These are the small crystals of triple phosphate, modifica- 
tions of the typical triangular prism, with its beveled ends, 
in which the body of the prism, instead of being a parallelo- 
gram, is nearly square, and in which the line connecting the 
beveled ends is exceedingly short, but rarely so short as 
not to be seen by careful focusing. The nature of the crys- 
tals may, however, be determined by the characteristic 
shape of the larger crystals about them, for they never 
occur alone. As previously mentioned, the octahedron of 
calcium oxalate is usually a square crossed by two diagonal 
lines, and therefore has the appearance of an envelop. The 



222 URINARY SEDIMENTS. 

phosphate crystals are promptly dissolved by acetic acid, 
while those of the oxalate of lime are insoluble in this acid. 

Clinical Significance. — Crystals of calcium oxalate may 
be found in the urine of persons who are typically healthy, 
as well as in certain diseased conditions. In health the 
presence of an oxaluria is dependent upon the cliaracter of 
the food ingested. Thus, it often follows the ingestion of 
rhubarb, onions, sorrel, tomatoes, grapes, and the like, 
because of the amount of oxalic acid contained in these 
substances. It is of frequent occurrence in various dis- 
turbances of digestion. It often follows the abundant 
ingestion of carbohydrates, and the use of an excessive 
meat diet ; this is especially the case when there is any 
interference with the oxidizing power of the system. We 
know that oxalic acid is formed as an intermediate product 
of the metabolism between uric acid and urea; that the 
process of formation appears to be one of oxidation which, 
if diminished, results in an oxaluria. Thus, in diseases of the 
heart and lungs an oxaluria is of frequent occurrence. It 
is commonly seen in diseases of the nervous system, and it 
is claimed by some that the oxalic acid present in the 
blood, on account of its poisonous action, causes a certain 
train of symptoms of which nervous phenomena are espe- 
cially prominent. This constitutes the theory of so-called 
^^ oxalic- acid diathesis y It is true that oxalic acid, when 
taken internally in considerable amount, exerts a poisonous 
action upon the organism, not only locally on the digestive 
tract, but upon the heart and nervous system. However, 
further evidence is necessary to prove that the symptoms 
of the so-called " oxalic-acid diathesis " are directly due to 
an increased formation of oxalic acid, or its retention in the 
blood. 

The primary crystals of calcium oxalate often set up a 
more or less marked irritation of the urinary tract, espe- 
cially if they separate from the urine in the kidney or renal 
pelvis ; the mechanical action is usually much less severe 
if the crystals separate in the bladder. The irritation 
thereby may be very severe and even be accompanied by 
abundant hemorrhage. Such a severe mechanical disturb- 
ance is invariably accompanied by pain, often frequent and 
painful micturition, and usually by a more or less concen- 
trated urine. If the separation of these primary crystals con- 
tinues for some time, the tendency to a calculus-formation 



CYSTIN. 22,5 

in the pelvis of the kidney or bladder is very great and 
especially in those cases in which there is more or less 
hemorrhage. 

In the more severe forms of oxaluria the condition has 
been incorrectly termed *' false Bright's disease," owing lo 
the extreme nervous symptoms, emaciation, dry skin, con- 
stant pain or a sense of weight across the loins, frequency 
of micturition, and other symptoms similar to those that 
accompany a nephritis. 

Cystin. — Cystin, (C3HgNS02)2, is an amido-acid, and con- 
stitutes one of the rarer forms of abnormal urinary sedi- 
ments. It crystallizes in the form of colorless hexagonal 
plates (Fig. 32), the angles of which measure about 120 de- 
grees. The sides of these plates are usually equal, although 
rarely two sides are found to be longer or shorter than the 



o 




o ® 



O 



Fig-. 32.— Cystin crystals. 




other four. It also crystallizes in quadrilateral prisms or 
groups of prisms. Crystals of cystin have an opalescent 
luster, and are often arranged in rosettes. 

Cystin is insoluble in water, alcohol, and ether ; also in 
acetic and tartaric acids. It is soluble in mineral acids and 
oxalic acid, in ammonic hydrate and other alkaline hydrates 
and carbonates, but is insoluble in ammonic carbonate. It 
is readily precipitated from its alkaline solution by acetic 
acid. Its solutions rotate the plane of polarized light 
strongly toward the left. 

Cystin contains 26 per cent, sulphur, the odor of sul- 
phuretted hydrogen being evolved when a urine containing 
cystin undergoes ammoniacal fermentation. 

Cystin is probably not a normal constituent of the urine, 
although Goldmann and Baumann claim to have isolated 
a substance resembling cystin, in very small quantities as 



224 URINARY SEDDIENTS. 

a benzoyl compound from normal urine. Under pathologic 
conditions the quantity of cystin in the urine undergoes 
considerable variation at different times, and it may tem- 
porarily disappear. The daily quantity may reach as high 
as 1.5 grams (Toel) ; ordinarily, however, it varies between 
a few milligrams and one gram. 

Cause of Cystimuda. — Until recently the cause of cystin- 
uria was thought to be due to abnormal processes of oxida- 
tion in the liver, since, in some respects, cystin resembled 
taurin. Marowski ^ considered it a vicarious elimination 
of taurin because in his case there was an absence of bile 
in the intestine. 

The experiments of Baumann and v. Udranszky, Brieger, 
and others, threw new light on the causation of this condi- 
tion. They found that certain products of intestinal putre- 
faction, called diamines, were eliminated in the urine and 
feces of persons afflicted with cystinuria. Baumann and 
v. Udranszky ^ made frequent examinations of the urine of 
a case of cystinuria for diamines, and found them regularly. 
They were isolated in the form of a benzoyl compound, 
which varied in amount from 0.2 to 0.4 gram in twenty- 
four hours. Approximately, one-third to one-fourth of 
these substances existed as tetramethylendiamine, and the 
remainder as pentamethylendiamine. ^ x\ccording to Brie- 
ger, since these diamines arise only as a result of putre- 
factive processes due to specific bacteria, cystinuria can be 
considered the result of a specific infection of the intestine. 
In Baumann' s case both diamines were invariably found in 
the feces as well as in the urine, and he observed that the 
relative amounts of these substances in the feces, especially 
the cadaverin, varied inversely as those in the urine. 
Neither Brieger nor Baumann was able to discover these 
diamines in the feces of healthy individuals, or in those 
suffering from other diseases.^ 

So far as has yet been determined, no definite relation 
exists between the formation of cystin and the diamines, 

^ "Deutsches Archiv f. klin. Med.," IV, S. 449. 

2 "Zeitschr. f. physiol. Chem.," 1889, XIII, S. 562. 

3 Brieger gave new names to these two substances, calling the first *'pu- 
trescin," and the latter "cadaverin." 

^ According to Neubauer and Vogel, these diamines have been found in the 
intestinal discharges of patients with Asiatic cholera. 



CYSTIN. 225 

although the same conditions that produce diaminuria 
usually also produce cystinuria. 

Clinical Significance. — Hereditary predisposition certainly 
appears to have some bearing as a cause, since so many 
cases have been reported of the existence' of the affection 
in several members of the same family. It is difficult, 
however, to explain the hereditary transmission of cystin- 
uria by the theory of Brieger, unless we assume that such 
individuals are more susceptible to the action of the "■ spe- 
cific bacteria" that produce the intestinal putrefaction than 
others. 

Cystin is met with in the urine of both infants and adults, 
but only rarely occurs in old age. It does not appear to 
be connected with any local or constitutional disease. It 
may be present and continue for years without any notice- 
able impairment of health, although, as a result of its sepa- 
ration from the urine, there is usually more or less irritation 
of the urinary tract. It has been occasionally observed in 
cases of liver disease, and Ebstein has noted the presence, 
of cystin in the urine of cases of acute articular rheumatism. 

The danger of a calculus-formation always attends the 
separation of cystin from the urine inside the body. Where 
a concretion exists, it is usual to find few (sometimes many) 
isolated crystals of cystin. 

Detection. — The detection of cystin is based chiefly on the 
recognition of the characteristic crystals in the urinary 
sediment ; also their solubility in weak ammonic hydrate, 
and their recrystallization upon the evaporation of the 
ammonic hydrate. 

It is always important to distinguish between the crystals 
of cystin and other like crystalline elements. Cystin can be 
differentiated from the pale, six-sided crystals of nric acid 
by allowing a drop of weak ammonic hydrate to mingle 
with the deposit on a glass slide, when either form of crys- 
tal will disappear ; evaporate, and if cystin be present, the 
crystals reappear ; if uric acid be present, crystals of ammo- 
nium urate will be found, instead of those of uric acid. 
Another simple method consists in treating the crystals 
with hydrochloric acid, which readily dissolves the cystin, 
but leaves uric acid unchanged. Cystin is distinguished 
from triple phosphate by its behavior with acetic acid, which 
quickly dissolves the phosphate crystals while those of cys- 
tin remain unchanged. 
15 



226 URINARY SEDIMENTS. 

The evolution of sulphuretted hydrogen from the urine 
should always lead to an examination for cystin, although 
H2S is by no means always due to the presence of cystin. 
Frequently, silver coins carried in the pockets of persons 
suffering from cystinuria are blackened by the sulphuretted 
hydrogen evolved, owing to the fact that cystin is some- 
times eliminated by the skin, where it decomposes and fur- 
nishes H2S.^ 

Bilirubin and Hematoidin. — Bilirubin is frequently de- 
posited in a urine containing bile in an amorphous or crys- 
talline form. The crystals of bilirubin (Plate 7) have two 
forms — (i) clusters of needles arranged as stellates, occur- 
ring either free in the urinary sediment or found attached to 
cells ; and (2) minute rhombic tablets or plates which vary 
in color from a yellow to a beautiful ruby red. 

They are soluble in caustic soda, and on the application 
of a drop of nitric acid a green rim forms about them. 

Hematoidin^ a derivative of hematin, was first discovered 
by Virchow in extravasated blood. It resembles bilirubin 
as closely in appearance as in its chemic properties. The 
crystalline formation of the two is identical. (Plate 7.) 
According to Hoppe-Seyler, v. Jaksch, and others, they 
are in all respects indistinguishable, and it is, therefore, safe 
to say that they are one and the same substance occurring 
under varying conditions. 

As previously stated, these crystals are very commonly 
found in urine containing bile ; it is not uncommon to find 
them in the urinary sediment following an extensive hemor- 
rhage, or the evacuation of an abscess, or pyonephrosis in 
which there has been hemorrhage. Ley den found these 
crystals in nephritis gravidarium ; Foltanek and Rosenheim 
in acute yellow atrophy ; and v. Jaksch in phosphorus- 
poisoning, cirrhosis of the liver, as well as in severe jaun- 
dice of the most distinct types. The author has occasion- 
ally met with these crystals in hemorrhage from the pros- 
tatic region, once in cancer of the bladder, and twice follow- 
ing a traumatic hemorrhage from the kidneys, as well as 
in jaundice from various causes. 

Leucin. — Leucin, CgH^gNOg, — amidocaproic acid, — is 
one of the products of decomposition of proteid bodies or 
of their derivatives, and is formed by the activity of certain 

1 For the quantitative determination of cystin see Neubauer and Vogel, 
•"Analyse des Harns," Bd. I, 1898, S. 807. 



Plate 7 






Hematoidin (Bilirubin) Crystals. 



LEUCIN. 227 

ferments, especially trypsin. As a urinary deposit it is of 
very rare occurrence. It is usually accompanied by crys- 
tals of tyrosin. 

Leucin occurs as highly refractive spherical crystals, 
which are usually marked with radiating and concentric 
striae. (Fig. 33.) When pure, it crystallizes in very delicate, 
small plates, often of irregular shapes and with a greasy 
feel, and are usually arranged in groups or found lying one 
upon another. When very impure, they appear as yel- 
lowish, highly refractive globules, apparently without crys- 
talline structure. In this form they may be mistaken for 
oil-drops, but by careful study it will be found that they 
are less highly refractive than oil-drops — i. e., not possess- 
ing quite so wide a dark border. 

Leucin, when pure, is difficultly soluble in cold, but more 




Fig- 33- — Leucin crystals. 

readily soluble in hot, water ; it is only sparingly soluble in 
alcohol ; readily soluble in acids and alkaline hydrates, and 
insoluble in ether. When impure, its solubility is distinctly 
increased. Leucin sublimes without melting when heated 
to 170° C. ; at a higher temperature it is decomposed into 
carbonic acid and amylamin. It combines with bases and 
acids to form salts. It can be obtained artificially by decom- 
posing proteids with acids. 

Detection. — Leucin may be recognized by the character- 
istic microscopic appearance of its crystals. Having found 
crystals resembling leucin, confirmatory tests should always 
be employed. 

I. When leucin is evaporated on a platinum foil with 
nitric acid, a colorless residue remains, which, if treated 



228 URINARY SEDIMENTS. 

with a few drops of sodic hydrate and heated, furnishes, 
according to the purity of the leucin, a watery, or more or 
less colored, fluid. If this fluid be concentrated, there re- 
mains an oily fluid that does not adhere to the platinum, 
but collects in drops of varying size (Scherer). 

2. On the addition of a trace of chinon and a few drops 
of sodic hydrate to a cold aqueous solution of leucin a 
marked violet color appears. Other amido-acids, as well 
as certain proteid bodies, give this reaction (Wurster). 

3. Leucin does not give a color reaction with furfurol, 
but tyrosin, on the other hand, gives a decided reaction 
with an aqueous solution of this substance. 

Since leucin nearly always accompanies tyrosin, its 
clinical importance will be considered under the subject of 
tyrosin. 

Tyrosin. — Tyrosin, C^H^^NOg, like leucin, is one of the 
products of the decomposition of proteid substances. It 
crystallizes in the form of exceedingly fine needles, which 
are arranged in sheaf-like collections, often crossing each 
other, and intersecting at their constricted middle portions. 
It also crystallizes in rosettes with the needles radiating from 
their centers (Fig. 34), especially if crystallized from an 
alkaline solution. 

The crystals are colorless, but when arranged in masses, 
often look dark, especially near the central portions, because 
of the compact arrangement of the needles. They are 
tasteless and odorless, very sparingly soluble in cold water 
(i : 2000 at 20° C), but much more soluble in boiling 
water (i : 150). They are almost insoluble in strong alco- 
hol (i : 135,000), quite insoluble in ether, and readily solu- 
ble in acid, alkalies, and solutions of the alkaline salts. 
Tyrosin readily combines with bases and acids to form dis- 
tinct compounds. (For details see Neubauer and Vogel, 
''Analyse des Harns," Bd. i, 1898, S. 281.) 

Tyrosin that has been isolated from the urine or other 
fluids is readily recognized, even when present in very small 
amounts, by means of Hoffinann's and Piria's tests. 

Hoffmann' s Test. — When a solution of tyrosin or a sus- 
pected deposit that has been boiled with an excess of water 
is heated with Millon's reagent, a bright crimson or pink 
color is produced. If much tyrosin be present, a similarly 
colored precipitate forms, while the supernatant fluid remains 
red, or sometimes a purple-red. 



TYROSIN. 



229 



Piria' s Test. — If tyrosin be treated on a watch-glass with 
a Httle concentrated sulphuric acid, and heated on a water- 
bath for from five to ten minutes, there results a compound 
— tyrosin-sulphuric acid — which has a pink color. This 
pink solution is then diluted wuth water, warmed, neutral- 
ized with barium carbonate, and filtered while hot. The 
colorless and neutral filtrate is then treated with a few drops 
of a very dilute solution of perchloride of iron, which pro- 
duces a violet color. An excess of the iron salt should be 
avoided, as it readily destroys the color. 

According to v. Udranszky,^ a characteristic reaction is 
obtained when an aqueous solution of furfurol is added to a 
solution of tyrosin. 




Fig. 34. — TjTosin crystals. 



Ftufurol Reaction. — Dissolve a small crystal of tyrosin 
in I c.c. of water, add one drop of a 0.5 per cent, solution of 
furfurol, and then underlie with concentrated sulphuric acid ; 
the fluid is colored rose-red. The mixture should not have 
a temperature above 50° C. 

The foregoing tests for tyrosin can not be applied directly 
to the urine with satisfactory results, since various urinary 
constituents either give -the same reactions or obscure the 
tests. It is, therefore, necessary to isolate the tyrosin, which, 
according to Blendermann,^ can be accomplished in the fol- 
lowing manner : 

Precipitate the urine with basic acetate of lead, filter, and 



1 " Zeitschr. f. physiol. 

2 *' Zeitschr. f. physiol. 



Chem.," XII, 355, 1888. 
Chem.," VI, 260, 1882. 



230 URINARY SEDIMENTS. 

remove the lead from the filtrate by passing sulphuretted 
hydrogen through it. Filter, and evaporate this filtrate to 
a very small volume, and allow it to stand several hours to 
crystallize. Filter, dissolve the crystals in boiling water, and 
apply the tests as directed. 

If the urinary sediment contains crystals that resemble 
ty rosin, their presence should always be confirmed as fol- 
lows : Filter off the sediment, wash with water, dissolve 
while still on the filter in hot ammonic hydrate to which 
some ammonium carbonate has previously been added, evap- 
orate the filtrate to crystallization, and examine microscop- 
ically. 

Care should be taken not to mistake the large hedgehog 
and sheaf-like crystals of acid urate of ammonium, also 
the sheaf-like crystals of acid sodium urate, for the rosettes 
and sheaves of tyrosin. 

Clinical Significance. — Leucin and tyrosin are constantly 
formed as products of the digestion of proteids, particularly 
by the action of trypsin, and usually, if not always, occur 
together. The presence of these substances in the urine is 
of very rare occurrence. It is claimed by some observers 
that they are present in minute traces in normal urine. 
This, however, is still an unsettled question, as certain reli- 
able observers have been unable to confirm such claims. 

Leucin and tyrosin have been found in the urine in con- 
siderable amounts in acute yellow atrophy of the liver and 
in acute phosphorus-poisoning. They have also been ob- 
served in the urine in cases of severe typhus fever, severe 
smallpox, and diseases of the intestines. The appearance 
of these two substances in disease is invariably accompanied 
by a very marked reduction in the quantity of urea. 

Cholesterin. — Cholesterin, C.,.H,.0, is a monatomic 
alcohol that is normally present in nervous tissue, blood- 
corpuscles, bile, and elsewhere. It occurs pathologically 
in gall-stones, as well as in atheromatous cysts, in pus, in 
tubercular masses, old transudations, excrements, and 
tumors. 

Cholesterin is probably not a constituent of the urine 
in health, and only occurs in this fluid under pathologic 
conditions. It crystallizes in large, colorless, transpar- 
ent plates (Fig. 35), whose angles and sides frequently 
appear broken, and whose acute angles are often from ^6 
to 87 degrees. In large quantities it appears as a mass 



CHOLESTERIN. 



231 



of white plates having a luster resembling mother-of-pearl, 
and a greasy feel. 

Cholesterin is insoluble in water, dilute acids, and alkalies. 
It is easily soluble in boiling alcohol, and recrystallizes 
on cooling. It is readily soluble in ether, chloroform, 
and benzol, and also in the volatile and fatty oils. It is 
dissolved to a slight extent by alkaline salts of the bile 
acids. 

Cholesterin crystals are only found in the urinary sedi- 
ment in cases of extensive fatty degeneration of some part 
of the urinary tract, as, rarely, in cases of subacute glomer- 
ular nephritis and chronic diffuse nephritis, and still more 
rarely during the fatty stage of an acute nephritis ; also in 
case of the evacuation of an abscess into the urinary tract. 




Fig. 35. — Cholesterin crystals. 



Detection. — If a mixture of five parts of sulphuric acid 
and one part of water acts on a cholesterin crystal, first a 
bright carmine-red and then a violet color appears. This 
fact is used in the microscopic detection of cholesterin. 
Another test consists in treating the crystal first with dilute 
sulphuric acid and then with a solution of iodine. The 
crystals will be gradually colored violet, bluish-green, and 
finally a beautiful blue. 

Salkozvski' s Reaction. — Cholesterin is dissolved in chloro- 
form, and then treated with an equal volume of concen- 
trated sulphuric acid. The cholesterin solution becomes 
first bluish-red, then gradually violet-red, while the sul- 
phuric acid appears dark red with a greenish fluorescence. 

Cholesterin is readily detected in the urinary sediment by 
means of the microscope. 



232 URINARY SEDIMENTS. 



ORGANIZED SEDIMENTS. 



The organized or anatomic sediments consist of formed 
elements coming from various parts of the urinary tract. 
Some of these elements are present in the urine under 
normal conditions, while others are found only as the result 
of functional disturbance or disease. 

Blood. — Red blood-corpuscles in the urinary sediment 
are always abnormal constituents, and indicate a pathologic 
condition in some portion of the urinary tract. Not infre- 
quently, in the female, blood enters the urine from the 
genital tract ; under such circumstances it is quite unim- 
portant. 

Blood-corpuscles vary in their microscopic appearance 
according to the character of the urine in which they are 
found, the length of time they have been in the urine, and 
the location of the urinary tract from which they come. 
Red blood-corpuscles are conveniently divided, for the pur- 
pose of urinary examination, into two classes — i. e.^ (a) 
normal and {U) abnormal blood globules. 

(a) Normal Blood. — This refers to the unaltered blood- 
corpuscles, which are so characteristic in appearance that 
there is very little, if any, danger of mistaking them for other 
elements in the sediment. They consist of biconcave discs, 
which always have a yellow color. (Fig. 36, left half) They 
are smaller than a leucocyte, being about -g-j^o- of an inch 
(between 7 and 8 micromillimeters) in diameter, free from 
nuclei, and perfectly homogeneous — that is, free from gran- 
ules and other visible cell-contents. These biconcave discs 
undergo a reversal of light and shadow on careful focusing, 
the center and periphery alternating in brightness or shadow 
as the objective is approximated to the slide or removed from 
it. Normal blood globules that have been in the urine for 
some time begin to undergo a change. Their edges often 
become irregular and crenated, — the so-called crenatcd blood- 
corpuscle, — found particularly in urines that contain a rela- 
tively large proportion of sodium chloride. This form still 
has more or less color, and belongs to the class of normal 
blood. In fact, any blood-corpuscle that has the slightest 
yellowish tint can be considered a normal blood-corpuscle. 
Within a few hours after the blood enters the urine the cor- 
puscle begins to swell and lose its color and density, and 
it is then that we have the — 



BLOOD. 233 

(b) Abnormal Blood Globules. — These are merely 
blood rings or shadows. (Fig. 36, right half.) The blood 
globule that was formerly biconcave is now biconvex — in 
other words, is swollen and has become a sphere, devoid of 
color or, if any color, the slightest tint of brown at the 
margin. The corpuscle has also become reduced in diam- 
eter, being only about two-thirds of the diameter of the 
normal blood-corpuscle. There are various forms of cor- 
puscles in the change from normal to abnormal blood, but, 
since the color is the criterion, any blood-corpuscle that has 
lost its yellow color is abnormal. 

A urine containing noi^mal blood is usually more or less 
reddish in color, depending upon the quantity present. If 
the amount of blood is excessive, it produces in alkaline 
urine a bright-red color (oxyhemoglobin), and in highly 
acid urine more of a brownish-red color (oxy- and methe- 



O. 0^_ " o'^J^o 






Fig. 36.— Blood-corpuscles : a, Normal ; d, abnormal. 



moglobin). Abnormal blood, when present in considerable 
quantity, imparts a brownish or smoky color (methemoglo- 
bin and hematin) to the urine. If present in large amounts, 
the color is usually very dark and may be black. If 
the quantity of either normal or abnormal blood in the 
urine be small, the color may give no indication of its 
presence, and under such circumstances is not usually de- 
tected until the sediment is examined microscopically. 

A distinct reaction for albumin is always obtainable in a 
urine containing blood, even though the quantity of blood 
be extremely small. 

Treatment of a Sediment Containing Blood. — The presence 
of a large amount of blood in the urinary sediment gener- 
ally completely obscures other formed elements ; on this 
account the blood globules must be destroyed. The de- 
struction of blood is best accomplished in the following 
way : 



234 URINARY SEDIMENTS. 

Allow the urine to settle thoroughly in a urine glass, then 
decant the supernatant bloody fluid, and to the sediment re- 
maining in the glass add a large volume of lukewarm water 
and a few drops of dilute acetic acid. Stir thoroughly with 
a glass rod, breaking up all clots, and allow the fluid to 
settle again. Repeat this process until the wash-water is 
practically free from blood pigment. Finally, settle and 
examine. The blood pigment will be found to have been 
washed from the blood-corpuscles, leaving a veiy fine net- 
work of abnormal blood globules and fibrin, in which other 
formed elements, such as casts, epithelium, etc., are capable 
of detection. 

The fact that a urine containing a large quantity of blood 
always contains a considerable number of leucocytes should 
be borne in mind, especially in drawing inferences as to the 
presence or absence of a suppurative process that is associ- 
ated with hemorrhage. If the leucocytes are numerous — 
in. fact, abundant — and more or less arranged in clumps, 
suppuration in some part of the urinary tract is highly 
probable. 

" Hematuria " is the term applied to a urine that contains 
blood, — that is, the blood-corpuscles together with the 
blood pigment, — and should not be confounded with the 
term '' hemoglobinuria," which applies to a urine containing 
blood pigment without blood-corpuscles. (See p. 364.) 

Clmical Significance. — The first interest in connection 
with a hematuria is to locate the source of the hemorrhage. 
Blood in the urine may come from the kidney, pelvis of 
kidney, ureter, bladder, prostate, or urethra. Blood com- 
ing from the genital tract of the female should in all cases 
be distinguished from that coming from the urinary tract. 

From the Kid^iey. — In fresh urine blood from the kidney 
is usually abnormal in character, and therefore imparts a 
more or less smioky color to the urine. Such urines after 
standing deposit a brown or coffee-colored sediment. But 
the blood may be normal, especially if from the straight 
tubules or in case of abundant renal hemorrhage when the 
urine is generally of a bright-red or brownish-red color, and 
upon standing furnishes an abundant blood-red sediment. 
Urines containing blood from the kidneys are generally 
acid in reaction, although if the amount of blood be very 
large, the reaction may be alkaline. Blood from the kidney 
is usually accompanied by renal casts, which often have the 



BLOOD. 235 

blood adherent ; and even blood-casts may be found. This 
fact constitutes an important element in diagnosis, since the 
only positive evidence of renal hemorrhage is the presence 
of blood on casts and true blood-casts. Blood-clots, usually 
of small size, are not infrequently found in the sediment in 
cases of abundant hematuria of renal origin. Large clots, 
however, are generally absent from the sediment unless they 
be of the long, slender, rod-like variety, which have been 
molded in passing through the ureters. In case the hemor- 
rhage is very slight blood-clots are usually not found in the 
sediment. 

The most frequent causes of blood from the kidney are 
the acute diseases and disturbances of this organ, such as 
active hyperemia (little blood), severe active hyperemia (con- 
siderable blood), and acute nephritis (large amount of 
blood). A very small amount of blood is sometimes found 
in the various chronic diseases of the kidney, but is generally 
so slight that it is unimportant. In all of the above-men- 
tioned kidney affections the blood is usually abnormal. In 
an exacerbation of an acute or an acute exacerbation of a 
chronic kidney disease the blood is generally abundant and 
normal in character, this condition being characterized by 
the sudden appearance of normal blood and a rapid fall in 
the twenty-four-hour quantity of urine. (See p. 300.) 
This form of renal hemorrhage is most common in the 
parenchymatous forms of renal disease, such as acute 
nephritis, subacute glomerular nephritis, and chronic diffuse 
nephritis. Hematuria is not uncommon in chronic inter- 
stitial nephritis as the result of vascular changes, including 
cardiac disease and atheromatous arteries. It is by no 
means rare in amyloid infiltration of the kidneys, on ac- 
count of the extensive infiltration about the smaller blood- 
vessels. 

In tuberctdosis of the kidney hemorrhage is a common 
symptom. The attacks are usually intermittent, although 
at times constant for a long period. An abundance of pus 
frequently accompanies a hematuria of this origin. A very 
thorough search for tubercle bacilli in the urinary sediment 
should always be made before eliminating this possibility 
of hemorrhage. New growths of the kidney also give rise 
to repeated attacks of hematuria, and at times the quantity 
of blood is profuse. There is generally more or less pus in 
the sediment, and also an abundance of small round and 



236 URINARY SEDIMENTS. 

degenerated cells. Such cases are to be recognized by 
renal tumor, more or less pain, and general cachexia of the 
patient. 

A calaihis in the substance of the kidney or in the renal 
pelvis of the kidney is a frequent cause of hemorrhage. 
The blood is generally accompanied by more or less pus. 
There is usually pain in the region of the affected kidney, 
tenderness on deep pressure, and pain extending down the 
leg or into the testicle. There may be renal colic when 
there is a small stone in the renal pelvis, the blood often 
being accompanied by small caudate cells from the super- 
ficial layer of the pelvis. In the light of these symptoms a 
hematuria resulting from a calculus should be suspected. 
The sediment should be carefully searched for crystalline 
deposits, which may or may not be present. 

The ingestion of certain drugs such as cantharides, tur- 
pentine, as well as certain other poisonous substances, may 
give rise to renal hematuria. It may also be due to trauma 
involving the kidneys, either directly as by wounds or 
blows, or indirectly from concussion. In tropical countries 
renal hematuria is frequently the result of an invasion of the 
kidney by a minute parasite — distoma haematobium. (See 
p. 269,) Of the various other causes of hemorrhage of renal 
origin, renal embolism, purpura haemorrhagica, hydatids, 
abscess, and cystic disease of the kidneys may be mentioned. 

From the Lower Urinary Passages. — Abundant hemor- 
rhage from the bladder is not uncommon, and \s most liable 
to be the result of one of three abnormal conditions — i. c, 
vesical calculus, tuberculosis, or new growth. A moderate 
amount of blood usually accompanies all acute and chronic 
inflammations of the bladder. Blood from the bladder is 
generally normal in character, but if present in small 
amounts, may be abnormal, particularly if the urine in 
which it is contained be highly acid or strongly akaline. The 
quantity of blood may be so abundant as to cause coagula- 
tion within the bladder or, as is more frequent, shortly after 
the urine has been voided. Blood-clots are more common in 
vesical hematuria than in other forms of hemorrhage, and 
are invariably associated with profuse bleeding. The clots 
are usually small and irregular in shape, but may be large 
and regular. A clot in the bladder may completely ob- 
struct the outflow of urine. Rarely, long, smooth, cord- 
like blood-clots are passed by the urethra. One instance 



BLOOD. 237 

of this was observed by the author, the clot being seventy- 
two inches in length. 

Blood of vesical origin is generally accompanied by more 
or less pus, and in cases of long-standing cystitis the urine 
is frequently alkaline, although not invariably so. For 
purposes of diagnosis the blood must be destroyed before 
microscopic examination is undertaken, and then a search 
made for characteristic cells of new growth, or crystalline 
elements ; or the sediment prepared, and carefully examined 
for tubercle bacilli. 

Hemorrhage from the neck of the bladder is probably 
most commonly the result of tuberculosis, although it may 
be due to various other pathologic conditions of this region. 
In most respects it resembles hemorrhage from the fundus 
of the bladder, although accompanied by symptoms sug- 
gestive of neck-of-bladder trouble. 

Hematuria of urethral origin may arise from traumatism, 
acute gonorrhea, urethral chancre, or following surgical 
operations on strictures of the urethra. The blood is gen- 
erally normal in character, and precedes the flow of urine, 
and also oozes from the meatus between the acts of mic- 
turition. 

Teichmatin's Test for Blood Pigment. — In the application 
of this test to urine it is necessary to coagulate the albu- 
min, which carries down with it the blood pigment. This is 
best accomplished for the purpose of this test (i) by 
strongly acidulating the urine with acetic acid, and then 
adding a saturated solution of sodium tungstate also acidu- 
lated with acetic acid. Upon heating this mixture a brown- 
ish precipitate of albumin and blood pigment is obtained, 
which is collected on a filter and dried. (2) The albumin 
can also be coagulated by boiling the urine, which has been 
faintly acidulated with acetic acid, as described on page 
T ^ T . This precipitate is placed on a filter, washed, and 
dried. 

Method. — A small portion of the dried and powdered pre- 
cipitate containing the blood pigment is placed on a micro- 
scopic slide, and moistened with a weak solution of potas- 
sium iodide or sodium chloride, and evaporated to dryness. 
The residue is covered with a cover-glass, and glacial 
acetic acid allowed to flow underneath in contact with the 
powder. This preparation is then gently heated until the 
acid begins to boil, when it is cooled, and examined 



238 



URINARY SEDIMENTS. 



by means of the microscope. If blood pigment be pres- 
ent, brown rhombic plates (Fig. 37) of iodide or chloride 
of hematin (also known as hemiyi crystals) will be found. 
These rhombic crystals are generally isolated, but they 
occasionally cross each other to form more or less charac- 
teristic groups. 

This test affords one very important means of determin- 
ing the presence of blood or blood pigment in the urine 
and other fluids of the body. It is also of great import- 
ance in distinguishing between the dark or black urines due 
to hemoglobin (see Hemoglobinuria, p. 364) and those 
that are dark or black from other pigments. Further- 




Figr- 37- — Teichmann's hemin cr>'stals. 



more, this test is of great practical value in the medicolegal 
detection of blood. 

Pus. — Pus-corpuscles, also termed leucocytes, are round, 
well-defined bodies, which are usually extremely gran- 
ular. (Fig. 38, (^.) They var}^ a little in size, but are 
usually quite constant and a trifle less than twice the size of 
the average normal blood globule. Although generally 
round, they vary somewhat in shape according to the age 
of the pus, the reaction of the urine, and the pathologic 
process that they accompany. Pus-corpuscles usually con- 
tain two or three nuclei, — polymorphonuclear leucocytes, 
— which constitute the chief characteristic of the typical 
pus-corpuscle. There is also the mononuclear leucocyte^ 
which is less common in the urinary sediment, and not 
easily distinguished from the small round cell. 



PUS. 239 

The nuclei of the pus-corpuscle are not usually distinct, 
on account of the very granular character of the body, but 
if the corpuscle be not decomposed or disintegrated, two 
or more nuclei can be made out upon focusing closely. 
The distinctions of the nuclei, and, in fact, the general 
appearance of the pus-corpuscle, depend largely upon the 
reaction of the urine in which they are contained and the 
age of the pus. 

In Acid Urine. — Fresh pus in an acid urine is very 
dense and the nuclei are seen with difficulty, if at all ; this 
constitutes the so-called '* normal piisy On the other 
hand, pus which has been suspended in the urine for some 
period, either within or outside the body, has a different 
appearance ; the body of the corpuscle becomes less distinct 
and the nuclei more prominent ; this is sometimes termed 



0. ^^ & m m 
® -^^ 

% 9 ® ® ® ® 

Fig. 38 — a. Pus-corpuscles as ordinarily seen ; d, ameboid pus-corpuscles ; c, pus-cor- 
puscles showing the action of acetic acid. 



'' abnormal pus,'' or '^ washed-oiit pus y In the abnormal 
pus-corpuscle the nuclei, instead of being separate bodies, 
are often fused, forming a single horseshoe-shaped nucleus, 
which is not so dense as the individual nuclei of the nor- 
mal pus-corpuscle. These abnormal pus-corpuscles may 
come from any part of the urinary tract, and are most com- 
mon in cases of long-continued chronic inflammation. 

In Alkaline Urine. — When a urine containing pus be- 
comes alkaline by a volatile alkali or alkaline hydrate, such 
as ammonium carbonate or hydrate resulting from the 
decomposition of the urea, the pus-corpuscles become de- 
stroyed. By the action of the alkali the pus becomes 
converted into a gelatinous, tenacious mass (see Donne's 
Test for Pus), which in many respects resembles white of 
^%'g. If a portion of this mass be examined microscopi- 



240 URINARY SEDIMENTS. 

cally, the pus-corpuscles will be found to have been de- 
stroyed, while only a dense mucus-like mass with adherent 
amorphous phosphates, crystals of triple phosphate, and 
bacteria remains. Some of the nuclei of the pus-corpus- 
cles may still be found. 

Pus-corpuscles are practically identical with the white 
corpuscles of the blood and lymph. In a fresh state they 
often present protoplasmic processes, — ameboid move- 
ments, — and under such circumstances should not be mis- 
taken for small caudate cells. 

It is very important to determine the exact nature of all 
small, round, or irregular bodies whose nuclei are not dis- 
tinct, to distinguish between leucocytes and small round 
cells, and also between ameboid leucocytes and small cau- 
date cells. This is best accomphshed by treating the urin- 
ary sediment with dilute acetic acid, as follows : Moisten 
the microscopic slide with a fraction of a drop of the acid, 
then place a drop of the sediment on the drop of acid ; 
mix thoroughly by means of a glass rod, and cover with 
a cover-glass. 

Action of Acetic Acid. — When dilute acetic acid (20 per 
cent.) is added to a fluid containing pus, the changes in the 
corpuscles are very rapid ; the first effect being to cause them 
to swell up, and next to dissolve the granules, the body of 
the corpuscle becoming smooth and the nuclei very distinct. 
In a short space of time the body of the corpuscle becomes 
almost invisible, W'hile the nuclei remain a much longer 
time. 

Epithelial cells are affected by acetic acid in much the 
same manner as leucocytes, but to a less marked degree. 
The first effect is a solution of the granules, making the 
nucleus very prominent, and, finally, after prolonged action 
of the acid, the cell begins to swell. The body of the cell 
does not usually become faint or invisible by the action of 
this acid. 

The action of water on the pus-corpuscle and epithelial 
cell is identical with that of acetic acid, except that it is 
very much slower and the stage of distinct nuclei is reached 
much later. 

Cliaracteristics of Urdne Contahiing Pus. — An acid urine 
containing pus is turbid except when the corpuscles are 
only few in number. It very soon deposits an opaque 
white sediment, which rapidly settles to the bottom of the 



PUS. 241 

sediment glass. This deposit should not be mistaken for a 
deposit of amorphous urates or phosphates. The distinc- 
tion is easily made by means of the microscope, also by 
the fact that the phosphatic deposit is readily dissolved by 
acetic acid, while the deposit of pus undergoes the changes 
already described. On the other hand, a deposit of amor- 
phous urates is readily dissipated by gentle heat. 

A purulent urine that has undergone alkaline fermenta- 
tion is invariably turbid and often contains a large, ropy 
mass, consisting of decomposed pus, etc., as previously 
mentioned. 

Do/iJies Test for Pus. — This depends upon the reaction 
that takes place between alkalies and the pus, and consists 
in the addition of an alkaline hydrate — potassic, sodic, or 
ammonic hydrate — to the suspected urine, or its sediment 
after the supernatant urine has been poured off. If pus 
be present, the urine becomes viscid, or the sediment is 
promptly converted into a viscid, gelatinous, mucus-like 
mass, which adheres to the bottom and sides of the test- 
tube. If some of this viscid substance be examined under 
the microscope, the pus-corpuscles will be found to have 
been destroyed or, rather, converted into the substance it- 
self If the action has not been very long or the propor- 
tion of the alkali to the pus is small, the outline of the pus- 
corpuscles may still be seen ; so, also, the nuclei of the 
corpuscles may still be discernible, embedded in the mucus- 
like mass. 

According to v. Jaksch, leucocytes are stained a deep 
mahogony-brown (glycogenic reaction) by a solution of 
potassic iodide. This serves to distinguish them from 
small round cells, which are stained a light yellow color. 

A. Vitali recommends the following test for pus : The 
suspected urine, if alkaline, is acidulated with acetic acid, 
and filtered through a thick filter. The deposit on the 
filter is then treated with a little guaiacum tincture, which 
has been kept in the dark. If pus be present, the inner 
surface of the filter takes a blue tint. The result is ob- 
tained even with a small number of leucocytes. 

Clinical Significance. — A perfectly normal urine may con- 
tain isolated leucocytes. It is only when they occur in 
considerable numbers or in conjunction with other formed 
elements (casts, etc.) that their presence becomes important. 

Pus is one of the most common elements found in the 
i6 



242 URINARY SEDIMENTS. 

urinary sediment. It may be derived from the substance of 
the kidney or pelvis of the kidney, the ureters, the bladder, 
the prostate gland, the urethra, or from the rupture of an 
abscess into some part of the urinary tract. Given, then, a 
urine containing pus, the first effort should be directed 
toward determining its source. The character of the ele- 
ments (cells, casts, etc.) that accompany the pus is of the 
utmost importance in locating the suppurative process. 

Pus coming from the kidney is found in cases of chronic 
suppuration in the tubules, such as may result from the 
presence of a calculus, the existence of a tubercular pro- 
cess, or the extension of an inflammation from the pelvis 
of the kidney into the renal tubules. In these conditions 
the pus is usually present in large quantity, and is some- 
times accompanied by a few or numerous renal casts, 
including pus-casts, which come from the suppurating area 
or the neighborhood of the diseased area in the kidney. In 
acute nephritis and following acute exacerbations of chronic 
renal diseases pus is usually present in greater or smaller 
quantities, and often found adherent to casts, but in these 
conditions true pus-casts are only rarely found. 

The diagnosis of abscess of the kidney can not be posi- 
tively determined until the abscess has evacuated its con- 
tents into the urinary passages. Previous to rupture of 
the abscess the urine usually presents evidences of a renal 
congestion — active hyperemia — that is going on in the renal 
tissue around the abscess pocket. A urine that suddenly 
contains a large quantity of greenish pus strongly suggests 
abscess of the kidney. 

In chro7tic pyelitis the urine is generally acid in reaction ; 
the pus is not only free, but is often arranged in clumps, and 
is mixed with small round cells from the deep layer of the 
pelvis of the kidney. Any obstruction to the outflow of 
pus causes a pyonephrosis ; if the back pressure becomes 
sufficient to force an opening, a sudden gush of greenish 
pus follows. So far as the author is aware an abundant 
deposit of greenish-colored pus is indicative only of abscess 
of the kidney, the evacuation of an abscess into the urinary 
tract, or pyonephrosis. 

Numerous leucocytes usually accompany an acute pye- 
litis, but ordinarily they are insignificant as compared with 
the other formed elements, which are, in themselves, diag- 
nostic. 



EPITHELIUM. 243 

Acute and chronic inflammations of the bladder — cystitis 
— are always associated with purulent urine. In acute cys- 
titis the urine is generally acid, but in chronic inflammation 
of this membrane the urine is often alkaline — ammoniacal 
— when voided. This is by no means true of every chronic 
inflammation of the bladder, since in tubercular cystitis and 
also in some cases of calculous cystitis the urine is acid in 
reaction. Purulent urines in general, and especially those 
from the bladder, readily become alkaline upon standing 
exposed to the air, if not already alkaline when voided. In 
cystitis the ropy, glairy mass consisting of decomposed pus, 
amorphous and crystalline phosphates, as well as epithelial 
cells, is not infrequently found. 

Pus from the neck of bladder or prostatic region is often 
found free, and arranged in clumps and mixed with neck- 
of-bladder cells. Oftentimes spermatozoa are found free 
and mixed with the pus in shreds. 

In urethritis the pus is usually very dense, and found 
chiefly in long threads or shreds, mingled with urethral 
cells, especially when of gonorrheal origin. When the 
amount of pus is abundant, it is generally free, no shreds 
being found. In acute gonorrhea the pus is usually yel- 
lowish in color. If any doubt exists as to the exact source 
of this pus, the question is often settled by directing the 
patient to pass the first portion of his urine into one ves- 
sel and the last portion into another ; if urethral, the first 
portion will contain much pus, while the second will be 
practically free from it. 

Pus from the uterus or vagina is usually accompanied by 
an abundance of squamous epithelium. If, in the case of 
a female, there is any doubt as to the source of the epi- 
thelium and pus, — whether bladder or vaginal, — a catheter 
specimen or one voided after a thorough vaginal douche 
should be procured. If pus be present in such a specimen, 
it must have originated in some portion of the urinary tract ; 
but if no pus be present, then it must have come from the 
genital tract. In blennorrhea a considerable quantity of pus 
may find its way into the urine. 

Epithelium. — Epithelial cells from various parts of the 
urinary tract usually form a part of the sediment of every 
normal and pathologic urine. Epithelium is the normal 
product of the mucous membrane, and represents the 
*' wear and tear " of such surfaces. In disease the desqua- 



244 URINARY SEDIMENTS. 

mation is usually much increased ; the recognition of the 
cells from the various parts of the urinary passages is, 
therefore, of the greatest importance, for it is often only by 
this means that abnormal processes can be located. The 
student should familiarize himself, as far as possible, with 
the cells that are characteristic of certain areas, before 
drawing inferences as to pathologic states ; he should also 
bear in mind that every normal urine contains a certain 
number of cellular elements. 

The epithelial cells found in the urinary sediment coming 
from a given part of the tract usually have entirely different 
shapes from those found in prepared histologic specimens 
of that part. For example, some of the renal epithelium 
/;/ situ is cuboid in shape, while that found in the urine is 
usually round. Other similar examples could be cited in 
which the shapes of the original cells have become changed, 
apparently by the action of the urine. 

In the detailed study of the cells that follows, the 
leucocyte will be used as a standard for comparison, since 
this body is nearly constant in size. (Fig. 39, a}^ 

Renal Epithelium. — These are epithelial cells from the 
tubules of the kidney. They are essentially small round 
cells, which are usually more or less granular, and present 
a single nucleus. (Fig. 39, ^.) There are three sizes of 
renal cells : i. e., the first, which is smaller than a leucocyte, 
and probably comes from the smaller tubules in the cortical 
portion of the kidney ; the second, which is about the same 
size as the leucocyte, and constitutes the average renal cell, 
which is probably from the convoluted tubules ; and the 
third, which is larger than the leucocyte, and probably comes 
from the straight or collecting tubules. Renal cells are 
frequently adherent to casts which, when practically covered 
with them, form the so-called epithelial cast. Renal cells 
are often veiy granular, and sometimes much distorted, as a 
result of degenerative processes in the kidney ; such are 
seen especially in cases of advanced chronic interstitial 
nephritis. 

Fatty renal cells are those which contain fat-drops (Fig. 
39, 0^, and are the result of degenerative processes in the 
tubules of the kidney. Such cells may contain only one or 
two fat-globules, or they may be entirely fatty degenerated. 
They do not usually differ in size from the renal cells 
already mentioned, and are not to be mistaken for the 



PELVIC EPITHELIUM. 245 

larger, so-called compound granule cell, to be described 
later. Not infrequently some or all of the fat is washed 
out of the cell, when it will be found to contain one or more 
vacuoles. Fatty renal cells are found in the urinary sedi- 
ment in cases of subacute glomerular nephritis, chronic 
diffuse nephritis, during the fatty stage of acute nephritis, 
and not infrequently in the severer forms of renal congestion. 

Renal cells always accompany renal casts, although at 
times they are present only in small numbers. Any small 
round cell that is adherent to a cast can be safely considered 
a renal epithelial cell. 

Pelvic Epithelium. — Epitheliar cells from the pelvis of 
the kidney vary in shape according to the parts from which 
they come, (a) Those from the superficial layer of the 
pelvis are small caudate cells. (Fig. 39, ^.) The tails are 
often curved and at times are bifurcated. The body is the 
same size or perhaps a little larger than that of the leuco- 
cyte, and usually has a distinct nucleus, a brown color, 
and is quite granular. These cells are sometimes arranged 
in groups, overlapping " like shingles on a roof," but are 
usually found singly. They are invariably accompanied 
by more or less blood, and indicate either a simple irritation 
of the renal pelvis or a more extensive inflammatory process 
— an acute pyelitis. They are of frequent occurrence, and 
often occur in very large numbers in cases of acute pyelo- 
nephritis, especially those cases that are of toxic origin. (U) 
The cells from the deep layer of the pelvis of the kidney 
are merely small round cells (Fig. 39, <^), usually about 
the size of the leucocyte, and having much the same appear- 
ance as the renal cells, although frequently not quite so 
dense. These cells are often arranged in clumps, and are 
always accompanied by pus which is both free and mixed 
with the cells in clumps. Deep pelvic cells are always 
found in cases of chronic pyelitis, {c) The cells from the 
calices of the kidney (Fig. 39, ^) are only rarely found in the 
sediment. They belong to the class of small round cells, 
but are considerably larger than the deep pelvic cells. They 
are also somewhat larger than the cells from the straight 
tubules of the kidney, and are generally found in clumps, 
overlapping one another. These cells have large, round, 
prominent nuclei, and are less granular than the cells from 
the deeper layer of the pelvis. They are usually found in 
cases of acute pyelitis. 



246 



URINARY SEDIMENTS. 



Ureteral Epithelium. — The author has had exceptional 
opportunities for the study of cells from the ureter in speci- 
mens obtained by the ureteral catheter. Epithelial cells 
from the ureter are of two forms (Fig. 39,/) — i. €., (i) 
small caudate cell, which is somewhat larger and denser 
than the cell from the superficial layer of the pelvis of the 
kidney, also with a larger and more prominent nucleus and 
a somewhat larger tail ; .and (2) a small spindle cell, which 
is generally very narrow and with a small nucleus. These 
two forms of cells are usually quite granular and small, and 




Fig. 39.— Epithelium from various parts of the urinar>' tract : a, Leucocyte (for 
comparison) ; b, renal cells ; c, superficial pelvic cells ; d, deep pelvic cells ; e, cells 
from calices ; y, cells from ureter; g,g.g,g^g, squamous epithelium from the blad- 
der ; h, h, neck-of-bladder cells ; i, epithelium from prostatic urethra ; k, urethral cells ; 
/, /, scaly epithelium ; m, m', cells from seminal passages ; w, compound granule cells ; 
o, fatty renal cell. 



should not be confounded with similar cells of larger size, 
which come from the bladder. The diagnosis of an inflam- 
matory process in the ureter is generally not easily made 
from the urinary sediment, since the number of cellular 
elements from this membrane is often small, and the in- 
flammatory condition is usually accompanied by either a 
pyelitis or a cystitis. In case there is marked irritation of 
the mucous membrane of the ureter by crystalline elements 
or small calculi, ureter cells may be found in large numbers, 
and the diagnosis more easily determined. 



BLADDER EPITHELIUM. 247 

Bladder Epithelium. — The epithelial cells from the 
fundus of the bladder are, for the most part, of the squamous 
or pavement variety. They are large, flat, thin, polygonal 
cells (Fig. 39, g), having a distinct and usually a central 
nucleus, which is prominent without the aid of acetic acid. 
When arranged in groups, the cells are frequently found 
joined by their edges and not overlapping, although at times 
they are found overlapping to a slight extent. Squamous cells 
from the bladder are generally moderately granular, but may 
be entirely free from granules. Those cells that come from 
near the openings of the ureters are usually large, thin, and 
circular in shape. EpitheHal cells from the month are not 
unlike those from the fundus of the bladder, but differ by 
having small nuclei and containing small particles of carbon. 
Cells from the mouth are generally clumped, and accom- 
panied by a large amount of mucin in which they are en- 
tangled, and often by particles of food. 

Epithelial cells from the neck of the bladder (in the male) 
are thicker, smaller, and much denser than those coming 
from the fundus. They are generally round or oval, and 
have a small, prominent nucleus. (Fig. 39, //.) They are 
usually not granular, and are from three to five times the 
size of a leucocyte. Cells from the neck of the bladder 
are often arranged in clumps of three or five, but are usually 
not found overlapping. An occasional cell from this region 
may be found in a perfectly healthy urine, but when found 
in excess with leucocytes, they indicate an irritation, and 
when mixed with pus. an inflammatory process at the neck 
of the bladder. 

Prostatic Cells. — Epithelial cells from the prostatic 
ducts are small round cells, which are not unlike renal cells 
in size. They are usually less granular and somewhat 
denser than renal cells, and present a single distinct nucleus. 
They are often adherent to long shreds of mucin, — so-called 
^^ prostatic casts,'' — and are generally accompanied by leuco- 
cytes and often by spermatozoa. 

Seminal Cells. — These are cells from the seminal 
passages, and are medium round cells, which are highly 
granular, rather dense, and contain an ill-defined nucleus. 
(Fig. 39, m, jji' .) Spermatozoa are often found within the 
body of the cell or projecting from it. These cells are in- 
variably accompanied by free spermatozoa. 

Urethral Cells. — Epithelial cells from the urethra vary 



248 URINARY SEDIMENTS. 

in shape according to the portion from which they come. 
Those from the prostatic portion are usually dense, pyriform, 
round, or irregular cells with a single distinct nucleus. 
(F^ig. 39, /.) They are smaller than those from the neck of 
the bladder, and from one and one-half to twice the size of 
a leucocyte. They are usually not clumped unless en- 
tangled in shreds of mucin with pus, as is often the case in 
stricture of this portion of the urethra. Cells from the 
pendidous portion of the urethra are either small round or 
small caudate in shape (Fig. 39, k), but somewhat denser 
than renal and superficial pelvic cells, but not so dense as 
those from the prostatic urethra. These cells are most 
frequently seen in the discharge that results from a gonor- 
rheal inflammation, and are usually intimately mixed with 
mucin and pus. The recognition of the cells from this 
portion of the urethra is of no great consequence, as the 
diagnosis of a urethritis is generally made by other means. 

Vaginal Epithelium. — The urine of the female nearly 
always contains more or less epithelium from the genital 
tract — that is, the vaginal secretion, generally consisting 
chiefly of epithelium with a greater or smaller number of 
pus-corpuscles, is washed from the vulva and often causes 
a very abundant sediment. Vaginal epithelium consists 
chiefly of the squamous or pavement form, although many 
other varieties of cells are usually present, such as the spin- 
dle, large and medium round, large and small caudate, and 
irregular cells. These cells are mononuclear, and usually 
only slightly granular, and generally somewhat larger than 
the average sized bladder cell. Vaginal cells are often 
arranged in large clumps, and on careful focusing will be 
found to be overlapping, " like shingles on a roof," and often 
several layers in depth. Very often the so-called scaly epi- 
thelial cell (Fig. 39, e^ is found, which represents the old 
epithelium from the vulva, and is a very thin, degenerated 
cell, containing only a remnant of a nucleus, if any nucleus 
at all. A urine holding a large amount of squamous epi- 
thelium and only a few leucocytes generally contains a 
vaginal secretion, which, in the majority of instances, is not 
abnormal. 

Compound Granule Cells. — These are medium and 
large round cells that have undergone complete fatty degen- 
eration. They are entirely filled with fat globules of vary- 
ing size, and do not show a nucleus. (Fig. 39, ;/.) Com- 



RENAL CASTS. 249 

pound granule cells should not be mistaken for fatty renal 
cells, the former bemg always larger than the latter, and 
usually more completely degenerated. Not infrequently 
they have prismatic or long hair-like crystals of the fatty 
acids protruding from them. They may be found free in 
the sediment, or adherent to casts. Compound granule 
cells are the result of extensive fatty degeneration, and 
come not only from the urinary tract but from other mucous 
membranes as well, especially those that are chronically 
diseased. When of renal origin, they are found in the 
sediment during the fatty stage of an acute nephritis, also 
in subacute glomerular and chronic diffuse nephritis, and 
rarely in active hyperemia. They may be found in the 
sediment in chronic pyelitis, chronic cystitis, chronic pros- 
tatitis, and in urethritis ; also as a result of ulcerations in any 
part of the urinary tract, and often in large numbers in the 
contents of an abscess or cyst cavity that has evacuated 
into the urinary passages. They are sometimes found in 
vaginal secretions, and also in expectorated matter that has 
been introduced into the urine. Compound granule cells 
are, therefore, of no great practical importance unless found 
in the presence of, and adherent to, renal casts. 

Renal Casts. — Renal casts, also termed ** tube-casts " 
and "cylinders," are molds of the uriniferous tubules. 
They are produced by the admission into the tubules of a 
coagulable (?) substance, which there solidifies, and, en- 
tangling whatever it may have surrounded in its liquid 
state, subsequently contracts, and is forced from the renal 
tubules by the urine. It is then carried into the pelvis of 
the kidney, thence into the bladder, and voided with the 
urine. 

The origin of renal casts has been the subject of much 
discussion and must still be considered an unsettled question. 

Three theories have been advanced as to their probable 
nature and mode of formation : 

(a) That they are composed of coagulable elements of 
the blood that have transuded into the renal tubules through 
pathologic lesions of the latter, and have there solidified, 
to be later voided with the urine as molds of the tubules. 

(b) That they consist of a secretion of the pathologic 
epithelium lining the renal tubules, this secretion solidifying 
to form molds or tube-casts, which are forced out by the 
urine. 



250 URINARY SEDIMENTS. 

(c) That they are the direct result of the disintegration 
of the renal cells, whose products become formed into casts 
of the tubules in which they are formed, and being forced 
out by the urine make their appearance in the sediment. 

The first theory (a) is the most plausible of the three ; 
at least, it is applicable to the nature and mode of formation 
of most of the casts found in the urinary sediment. 

Renal casts have been variously classified, but the 
simplest division is the following, which is based upon their 
microscopic appearance : 

r (i) Pure hyaline. 
I. Hyaline (transparent) casts < (2) Fibrinous. 



((3) Waxy. 

|(i) Fine. 
< (2) Coarse. 
( (3) Brown. 



I (i) Fine 
II. Granular " < (2) Coarse. 

III. Epithelial 

IV. Blood 
V. Fatty 

VI. Pus 

r(i) Urate. 
VII. Crystalline " < (2) Oxalate. 

I (3) Cystin. 
VIII. Bacterial 
IX. ''Mucous" (nucleo-albumin) casts, also termed 
/a/se casts. 

I. Hyaline Casts. — Hyaline^ casts are of three varie- 
ties : (i) Pure hyaline, (2) fibrinous, and (3) waxy casts. 

(/) Pure hyaline casts are pale, transparent, homogeneous 
cylinders, generally with rounded ends. (Fig. 40.) They 
may be short or very long, even extending through six or 
more fields of the microscope. ^ They are found of vary- 
ing diameters, some narrow and others wide, but always 
presenting a cylindric appearance. Their sides are usually 
parallel and straight, but they may be indented, presenting 
a scalloped appearance. They are often twisted upon them- 
selves, and not infrequently have a serpentine shape. One 
end of the cast may be ragged and irregular, showing that 
the original cylinder has been divided, and occasionally a 

^ The term hyaline is here used in the broad sense of transparent. 
2 Leitz microscope, No. I eye-piece and No. 7 objective. 



HYALINE CASTS. 251 

segment is seen with both ends ragged. Pure hyahne casts 
are free from granules, and are therefore often very difficult 
to detect in the sediment. They are best discovered by 
reducing the amount of light entering the microscope, 
either by manipulating the mirror, or by interposing the 
hand between the source of light and the mirror, thus shading 
the microscopic field. As a rule, the casts of large diameter 
are somewhat more refracting, and thus more readily de- 
tected than the small narrow casts. 

Not infrequently hyaline casts contain a few veiy fine 
granules of a pale color. They sometimes exhibit here and 
there upon their surfaces a renal cell or a blood globule or 
droplet of oil. Such casts are considered strictly of the 




Fig. 40. — Pure hyaline casts. 



hyaline order, and are referred to as hyaline casts with a 
renal cell or a blood globule or fat-drops adherent, as the 
case may be. 

The narrow hyaline casts doubtless have their origin in 
the smaller undenuded tubules, while those of large diameter 
come chiefly from the large straight, or collecting tubules of 
the kidney. In advanced disease of the kidney, notably 
chronic interstitial nephritis, we find an exception to the 
rule — /. e., the majority of the casts emanating from high up 
in the kidney are of large diameter, while those from the 
collecting tubules are very large. Such casts are from ex- 
tensively denuded tubules, the result of the advanced 
disease. 



252 URINARY SEDIMENTS. 

Hyaline casts are common to all diseases and disturbances 
of the kidney, and not pathognomonic of any one abnormal 
condition. They are, however, predominant in the sedi- 
ment in cases of chronic interstitial, chronic diffuse nephritis, 
amyloid infiltration, and in passive hyperemia ; while their 
relative proportion is much smaller in comparison with the 
other forms of casts present in active hyperemia, acute 
nephritis, and subacute glomerular nephritis. 

(2) Fibrinous Casts. — These are very dense or highly 
refractive casts, usually of the transparent variety and always 
of a yellowish color, which ranges between a pale yellow 
and a deep brown. (Plate 8.) 

Fibrinous casts are, however, sometimes granular, and 
often have renal epithelial cells and blood globules, and, 
not infrequently, oil-drops adherent. Like the pure hya- 
line casts, they are of various shapes and sizes, but being 
heavier and denser than the hyaline form, show a greater 
tendency to crack and break, thus becoming divided into 
rather short segments, the ends of which are usually thick 
and ragged. They are also frequently found of moderate 
length, with rounded ends ; they are, as a rule, of larger 
diameter than the average hyaline cast found in the sedi- 
ment. Fibrinous casts sometimes have so little color as to 
be distinguished with difficulty from the waxy cast that is 
always perfectly colorless. If any doubt exists in the mind 
of the observer as to their true character, the term " highly 
refractive casts " should be used, until, upon further study, 
the observer is convinced that they are fibrinous and not 
waxy casts. The bearing of this suggestion is seen in the 
following paragraph : 

Fibrinous casts usually accompany blood in the sedi- 
ment — in other words, are found in acute diseases or dis- 
turbances of the kidney, such as acute nephritis, and some- 
times active hyperemia ; also in acute exacerbations of 
either acute or chronic renal diseases. The fibrinous cast 
is simply one of the elements of an acute condition, and as 
this condition subsides, it disappears from the sediment. 
Fibrinous casts do not, therefore, indicate an unfavorable 
prognosis. Waxy casts, on the other hand, are practically 
unheard of in active hyperemia and acute nephritis, but are 
most often found in the sediment in the advanced forms of 
kidney disease, their presence being always an unfavorable 
prognostic sign. 



Plate 




Fibrinous Casts. 



HYALINE CASTS. 



253 



The X.Qxvi\ fibrinous as applied to these casts is inappro- 
priate, as they do not consist of fibrin, nor do they have 
any relation to it, only resembling fibrin in their yellow or 
brownish color. 

(j) Waxy Casts. — These, like the fibrinous casts, are 
very highly refractive casts of the transparent variety, and 
are always perfectly colorless. (Fig. 41.) They are usu- 
ally of large diameter and often very long, and their sur- 
faces may be marked by indentations showing imperfect 
vertical segmentations ; they often have a serpentine appear- 
ance. Not infrequently, waxy casts are coarsely granular, 
the granules apparently having the same composition as 
the cast itself. (Fig. 41.) They may have fat-drops, or fatty 




Fig. 41. — Waxy casts. 



renal cells, or compound granule cells adherent to them. 
On account of their thickness and density, waxy casts are 
often found with cracks on their surfaces, also frequently 
found in segments, with one or both ends rough and irreg- 
ular, showing that the long casts have become broken into 
several small pieces. 

Waxy casts should, in all instances, be distinguished from 
fibrinous casts, since, as has already been explained, they 
have an entirely different significance. 

Waxy casts are found in the sediment in the advanced 
stages of all chronic diseases of the kidney, such as chronic 
interstitial, chronic diffuse, and subacute (parenchymatous) 
nephritis, and are of bad omen, indicating that death will 



254 URINARY SEDIMENTS. 

probably occur within a comparatively short time, usually a 
year. This rule, however, is not invariable, as was well 
demonstrated by a case that the author observed for a 
period of over two years, in which waxy casts were con- 
stant, and, as was shown at the autopsy, there existed a 
marked chronic diffuse nephritis of the parenchymatous 
variety. Waxy casts are a frequent accompaniment of 
amyloid infiltration of the kidneys, in which the}^ appear 
earlier than in other chronic renal diseases, and are of de- 
cided diagnostic value. They are of much less importance 
as a prognostic sign than in other chronic renal affections. 

The term waxy, as applied to these casts, is a misnomer. 
It was formerly supposed that waxy casts were characteristic 
of amyloid infiltration of the kidneys, but, as has been 
shown, they are often found in other chronic diseases of the 
kidney. These casts rarely show the amyloid reaction with 
methyl -violet and with iodopotassic-iodide solution, even 
when amyloid disease of the kidneys is present. 

The hyaline cast constitutes the basis or groundwork of 
all other casts to be described, each cast being named 
according to the elements adherent to or embedded in it. 
Thus, a cast covered with granules is called a granular cast ; 
with epithelium, an epithelial cast ; with blood, a blood-cast, 
etc. 

II. Granular Casts. — These casts consist of a hyaline 
basis in which granules are embedded. Various terms are 
applied to these casts — /. e., when covered with fine granules, 
finely granular ; with coarse granules, coarsely granular ; 
and when the granules are colored so as to give the cast a 
brown color, browii granular^ etc. (Fig. 42.) 

The granules found on these casts probably come from 
the renal tubules, and are the result of the degeneration and 
disintegration of the renal epithelium. At times, these 
granules appear to result partly from the destruction of 
blood-corpuscles and leucocytes. This is particularly the 
case in connection with the brown gj^anular casts, which 
appear to derive their color from the blood pigment. Bile 
naturally stains granular casts yellow or it may give them a 
brown color. Brown granular casts nearly always accom- 
pany blood-casts. 

Granular casts, like the hyaline forms, have a variety of 
shapes, and may be of small, medium, or large diameter. 
They are usually rather short and have rounded ends ; not 



EPITHELIAL CASTS. 



255 



infrequently, however, fragments of granular casts are found 
with rough and irregular ends. They may have renal epi- 
theHum, blood globules, fat, or leucocytes adherent to their 
surfaces or embedded in them. 

Finely granular casts are found in every disease or dis- 
turbance of the kidney ; they, therefore, can not be con- 
sidered pathognomonic of any one disease or class of dis- 
eases. 

III. Epithelial Casts. — These are casts that are prac- 
tically covered with renal epithelium. (Fig. 43, I.) The 
renal cells may be embedded in, or firmly adherent to, 
either hyaline or granular casts. A hyaline cast that holds 
one, two, or three renal cells is best termed a hyaline cast 




Fig. 42. — a. Hyaline and finely granular cast ; b, finely granular cast ; c, coarsely 
granular cast ; rf, brown granular cast ; ^, granular cast with normal and abnormal 
blood adherent ; f, granular cast with renal cells adherent ; g., granular cast with fat 
and a fatty renal cell adherent. 



witli a renal cell or cells adherent ; the same applies to a 
granular cast. This term serves to distinguish such casts 
from those that are covered with renal cells and properly 
called epithelial casts. Renal cells on casts are usually 
more or less granular and swollen, and sometimes they are 
so firmly embedded in the cast that their outlines are ill 
defined. The nuclei of the cells often stand out prominently, 
although at times the cells are so granular as partially or 
entirely to obscure the nuclei. These cells may also con- 
tain fat globules. In an epithelial cast leucocytes are 
frequently found mixed with the epithelial cells ; such a 
cast, which consists chiefly of epithelium, should not be 
mistaken for a true pus-cast 



256 URINARY SEDIMENTS. 

Epithelial casts are most commonly found in those path- 
ologic conditions that cause an exfoliation of the renal 
epithelium, such as severe active hyperemia, acute nephritis, 
and subacute glomerular nephritis. They are only rarely 
found in the urine of chronic interstitial nephritis and amy- 
loid infiltration of the kidneys. In cases of extreme renal 
irritation and congestion the epithelial lining of the tubules 
is sometimes thrown off intact for short distances, an epi- 
thelial cylinder possessing a lumen resulting. 

IV. Blood-casts. — These are of two kinds — /. e., (a) a 
hyahne or granular cast, which is practically covered with 
blood globules ; and (b) the cylinder, which consists of 
coagulated blood — fibrin with blood globules firmly em- 
bedded. 

Blood-casts are found in the urine in those conditions in 




Fig-. 43. — I, Epithelial cast; 2, blood-cast; 3, pus-cast; 4, fatty cast; 5, fatty cast 
with a compound granule and fatty renal cell adherent (crystals of the fatty acids 
protruding). 



which there is more or less hemorrhage into the renal 
tubules. In the majority of instances the blood-cast is 
made up of abnormal blood (Fig. 43, 2), in which case the 
inference is that either the blood comes from high up in 
the kidney or the hemorrhage into the tubules is very slow. 
In casts of this kind the blood-corpuscles are unusually 
distinct, but, at times, indistinct, requiring careful focus- 
ing in order to make out the faint, deeply embedded 
globules. Not infrequently blood-casts consist of normal 
blood ; under such circumstances the hemorrhage is usually 
either from the pyramidal portion of the kidney — straight 
tubules — or is very abundant and from higher up in the 
kidney. These normal blood-corpuscles, which still have 
their pale-yellow color, are often observed agglutinated, 



FA'ITY CASTS. 257 

at times forming a solid mass on the cast. Ordinarily, 
however, they are not so agglutinated but that the outlines 
of the individual corpuscles can be readily seen. Blood- 
casts are generally short, of medium diameter, and quite 
uniform throughout, usually having rounded ends. One 
portion of the cast may be hyahne or granular, and the re- 
mainder covered with blood. 

Blood-casts are found in the urine in hematuria of renal 
origin, acute diffuse nephritis, acute renal congestion, and 
hemorrhagic infarctions of the kidneys. Blood-casts do not 
in themselves furnish positive evidence of organic renal dis- 
ease, since any hemorrhage from the kidney may be asso- 
ciated with blood-casts in the urine. On the other hand, it 
maybe stated that the presence of blood-casts constitutes the 
only positive evidence of the existence of renal hemorrhage. 

V. Fatty Casts. — These are casts that are thickly 
studded with fat drops. (Fig. 43, 4-) It has already been 
stated that a hyaline or granular cast may have oil globules 
attached, but the term fatty cast only applies to those that 
are practically covered with fat. At times, fine needle- or 
hair-like crystals of the fatty acids are found protruding 
from these casts, and they may have fatty renal cells and com- 
pound granule cells embedded in or attached to them. (Fig. 
43, 5.) Generally, the fat-drops are small and appear as 
glistening points ; such should not be mistaken for the less 
highly refracting granules not fat. Sometimes the globules 
are large, when they are easily recognized. Fatty casts indi- 
cate that a fatty degeneration of the kidney is in progress, 
since the fat is probably the result of extreme degeneration 
of the renal cell protoplasm. They are not necessarily in- 
dicative of a chronic kidney disease, although most common 
in subacute glomerular (chronic parenchymatous) and 
chronic diffuse nephritis. They are also found during the 
fatty stage of an acute nephritis, and occasionally in severe 
renal congestion. 

- VI. Pus-casts. — Pus-casts are those that are covered 
with pus-corpuscles or leucocytes. (Fig. 43, 3.) The cor- 
puscles are generally highly granular, and often so much so 
that their nuclei are entirely obscured. Under such cir- 
cumstances, because of failure to make out the nuclei, casts 
that are covered with pus-corpuscles are often considered 
to be epithelial casts. Such inference should not be drawn 
without first thoroughly treating the sediment with dilute 
17 



258 URINARY SEDIMENTS. 

acetic acid, which dissolves the granular matter, thus caus- 
ing the nuclei of the leucocytes and the nucleus of the 
cell to stand out prominently. 

Hyaline or granular casts with one, two, or three leuco- 
cytes adherent are frequently found in acute diseases and 
disturbances ; also in acute exacerbations occurring during 
the course of a chronic disease of the kidneys. True pus- 
casts, on the other hand, are quite uncommon, and, when 
present, indicate a chronic suppurative process in some 
portion of the kidney. Pus-casts may be formed in case 
there is an abscess of the kidney or tuberculosis of this 
organ ; also in cases of chronic pyelitis with extension into 
the straight tubules, in which instance they are usually of 
large diameter. 

Bacterial Casts. — True casts when covered with bacteria 
have received the name ''bacterial casts'' Accidental 
aggregations of bacteria that closely resemble renal casts in 
shape and size, and seen particularly in urines that have 
been exposed to the air for a long time, should not be mis- 
taken for bacterial casts. True bacterial casts closely 
resemble the brown granular casts, and are distinguished 
from the latter by their resistance to certain chemicals, such 
as acetic acid, mineral acids, and strong alkalies. It is 
almost impossible to distinguish between them by means of 
the microscope, particularly if the bacteria belong to the 
class of micrococci as is usually the case. Bacterial casts 
are very uncommon, and are chiefly found in the septic 
forms of renal disease, especially those accompanied by 
embolism, and are therefore a grave prognostic sign. They 
are sometimes found in the ascending form of chronic pyelo- 
nephritis or ''surgical kidney." 

VII. Crystalline Casts. — These are of three kinds, and 
are named according to the form of crystal adherent to or 
embedded in them. Thus, a urate cast is one that is 
covered with crystals of ammonium urate, usually the 
hedgehog crystals ; the cystin cast, covered with hexagonal 
crystals of cystin, as seen rarely in cases of cystinuria ; and 
the calcium oxalate cast, covered with the octahedral, oval, 
or dumb-bell crystals of calcium oxalate. As a rule, 
crystalline casts show that the crystals deposited thereon 
were separated in the kidney, and therefore primary. Occa- 
sionally, crystals are deposited on casts secondarily — that 
is, after the urine has been voided. 



FALSE CASTS. 259 

False Casts. — False casts, also termed mucin casts, 
shreds, or cylmdroids , are not infrequently found in the sedi- 
ment. They are long, flat structures, usually with fine, 
wavy, longitudinal striations, and long tapering ends. (Fig. 
44.) They are colorless, often twisted or folded, and 
usually free from adherent elements, although they may 
have cells, leucocytes, and blood globules adherent. False 
casts are usually longer than the true renal casts just 
described, and appear to be flat and not cylindric. It is 
probable that these structures consist only of coagulated 
nucleo-albumin or mucin, although the subject requires 
further investigation in order to determine their true nature. 
It is sufficient to say that they are, apparently, not true 
casts, that they are frequently present in a urine that is free 
from albumin, and that they are of little clinical importance. 

False casts may originate in the kidney, but they are 
most commonly found in the sediment in connection with 




Fig. 44. — False casts or cylindroids (after von Jaksch). 



irritation or inflammation of the lower urinary passages, 
particularly of the bladder, prostatic region, and urethra. 
They may be found in the prostatic ducts as a result of mild 
or severe inflammatory processes, when they are usually 
accompanied by a large number of mucin (nucleo-albumin) 
threads or shreds. It is often exceedingly difficult to dis- 
tinguish these so-called prostatic casts from true renal casts ; 
in fact, these two structures may exist in the same urinary 
sediment. 

Prostatic Plugs. — These bodies, occasionally found in 
the urinary sediment, are evidently formed in the prostatic 
ducts. They appear to be cylindric, often with rounded 
ends, and are usually of large diameter, but may be of 
irregular shape, as from a dilated duct or cavity. They are 
either colorless or colored yellow, when they have much 
the appearance of fibrinous casts. Prostatic plugs usually 
have spermatozoa embedded in them, and, at times, leuco- 



260 



URINARY SEDIMENTS. 



cytes or epithelial cells from the prostatic ducts are firmly 
adherent to them. 

These bodies are found most commonly in mild inflam- 
matory processes that involve the region of the neck of the 
bladder and the prostatic ducts. 

Spermatozoa. — Spermatozoa are frequently found in the 
urine of healthy men. They are bodies about 50 [jl in 
length, and consist of an oval head, or body, about 4. 5 ;>« 
in length, to which is attached a long, tapering whip-like 
tail of extreme delicacy. (Fig. 45.) When freshly ejected, 
they exhibit active eel-like movements, strongly suggestive 









^ 


%. 






- 












L 




c 




® 


c 





6 













c 


c 








Fig. 45. — Spermatozoa. 



of volition ; but as seen in the urine they are always 
motionless. The cause of the movements in spermatozoa 
is unknown, although Roberts claims that they are floating 
cilia and resemble the oscillating sperm-cells of the anther- 
idae of mosses. Their movements are arrested by water, 
alcohol, ether, drying, etc. They resist putrefaction, and 
when once dried, may, after years, be restored to their 
original form by moistening them with a weak solution of 
sodium chloride or potassium acetate. Spermatozoa are 
often accompanied by medium-sized, highly granular cells 
(Fig. 39, ;//, ni'^ ; also by finely granular cells with one or 
more nuclei ; more rarely, by lecithin corpuscles and sper- 
matic crystals. 



CORPORA AMYLACEA. 261 

Cli)iical Significance. — A certain number of spermatozoa 
necessarily find their way into the urine of both sexes 
after coitus ; also into the urine of men after involuntary 
nocturnal emissions. The persistent absence of spermato- 
zoa from the seminal fluid indicates sterility. The recog- 
nition of spermatozoa is most important in connection 
with medicolegal cases — suspected rape. Their presence in 
vaginal secretion soon after coition and in stains upon linen 
is easy of demonstration. Spermatozoa are sometimes 
found in the urine in cases of severe acute febrile disease, 
such as typhoid fever, pneumonia, and acute septic condi- 
tions, also following convulsions. They are of frequent 
occurrence in cases of acute or chronic prostatitis or irri- 
tation in the prostatic region. The condition of spermator- 
rhea is characterized by the constant presence of sperma- 
tozoa in the urine. 

Detection. — Spermatozoa are best detected by their char- 
acteristic appearance under the microscope. Florence,^ of 
Lyons, has recently described a characteristic reaction that 
takes place between iodine-potassium iodide and seminal 
fluid, and which is probably dependent upon the presence 
of cholin. 

Florence Reaction. — The reagent is prepared as follows : 

Potassium iodide, 1.65 grams. 

Iodine, 2.54 " 

Distilled water, 30 *' 

The iodine-potassium iodide in this mixture corresponds to 
the formula KI3. 

A small portion of the suspected seminal fluid is treated 
with a drop of the foregoing reagent. If semen be present, 
small, dark, rhombic crystals appear, which are very simi- 
lar in their general appearance to the hemin crystals ob- 
tained in Teichmann's test for blood. 

Corpora Amylacea. — The so-called amyloid bodies, or 
corpora amylacea, have somewhat the appearance of starch 
granules, but they differ from starch in their chemic re- 
actions. They are microscopic, spheroid, homogeneous, 
or lamellated bodies (Fig. 46), usually containing within 
them a core, which is also frequently lamellated and some- 
times colored. They do not swell when soaked in hot 

1 Florence, " Du Sperme et des Taches de Sperme en Medecine Legale," 
1897. 



262 URINARY SEDIMENTS. 

water, and are not split up by boiling with dilute mineral 
acids ; they are not dissolved by fuming nitric acid. Amy- 
loid bodies are colored red by methyl-violet, while starch 
is colored blue. When the former are treated with iodine 
or iodine-potassium-iodide solution, they not infrequently 
show a violet to a blue color, which becomes distinctly 
blue by the subsequent action of sulphuric acid. These 
bodies seem to have no connection with amyloid infil- 
tration, although they sometimes resemble its products. 
They may occur normally as well as under pathologic con- 
ditions, and are apparently of little clinical importance. 

Corpora amylacea are frequently found in the acini of 
the prostate gland, from which they may find their way 
into the urine, sometimes in large numbers. They are also 
found in the ependyma of the ventricles of the brain and in 





Fig. 46.— Corpora amylacea. 

areas of sclerosis of the brain and cord ; also in extravasa- 
tions of blood in various other situations. The amyloid 
bodies represented in figure 46 were found by the author in 
the urine of a man who, several days before, had had an 
extensive hemorrhage from the prostatic region. At the 
time these bodies were found, the urine was, however, free 
from blood. In the experience of the writer these so-called 
amyloid bodies are a rare constituent of the urinary sedi- 
ment. 

Amyloid Concretions. — These are frequently found in 
the prostate gland of old people. They are sometimes 
large enough to be detected with the naked eye, and are 
usually hard, and often have a dark color due to the depo- 
sition of pigment. (See Prostatic Concretions, p. 282.) 



EXTRANEOUS SUBSTANCES. 263 

EXTRANEOUS SUBSTANCES FOUND IN URINE* 

These are very numerous, and include, indeed, all sub- 
stances that are liable to get into vessels containing the 
urine. The most common of these are fibers of cotton and 
linen, hair of blankets, worsted, wool, human hair, cats' 
hair, splinters of wood, oil globules, starch granules, lyco- 
podium and other pollen, tea leaves, bread crumbs, particles 
of glass, dust, etc. It is a common custom with some 
persons to expectorate into the vessel that is to contain 
the urine or into the urine after it has been voided, hence 
pavement epithelium containing pigment granules, particles 
of food, free oil, etc., will be found. It is very important 
that the student should become familiar with the microscopic 
appearances of all these extraneous elements before he be- 
gins the examination of urinary sediments. 

PRESERVATION OF URINARY SEDIMENTS. 

In order to preserve urinary sediments it is necessary to 
treat the urine and its sediment in such a way as to prevent 
subsequent changes, of which the most common are ammon- 
iacal decomposition and the formation of vegetable growths. 
To accomplish this end, the coloring-matters and the salts 
of the urine must be removed by washing with those media 
that will take up the soluble urinary constituents and, at the 
same time, leave the sediment — cells, casts, crystals, etc. — • 
in the same condition as found in the fresh urine. 

Epithelial cells, renal casts, blood, pus, fat, and fibrin, 
are best preserved in the following manner : Allow the 
urine to settle thoroughly in a urine glass, or centrifugalize, 
and wash by decantation twice with a saturated aqueous 
solution (4 per cent.) of boric acid, and then three times 
with an aqueous solution of potassium acetate (specific 
gravity, 1030) containing ^ of i per cent, of formalin. 
The sediment is left in the last washing of potassium acetate 
and formalin, and is then placed in a tightly stoppered bottle, 
where it will keep for months and years. By this process 
the sediment suffers very little, if any, change, excepting 
that any blood that was originally in the sediment as 
normal blood will be changed to abnormal blood. 

Crystalline sediments on account of their solubility in the 
media already given require different treatment, the pre- 



264 URINARY SEDIMENTS. 

servative used varying with the form of crystal to be pre- 
served. 

Uric acid, calcium oxalate, hippuric acid, cyst in, and 
cholesterin crystals should be washed, by decantation, several 
times with a small volume of very dilute acetic acid (i to 2 
per cent) ; finally, after all of the soluble urinary salts have 
been removed, they are left in the last washing, which is 
then placed in a perfectly clean, tightly stoppered bottle. 

Acid ammonium iirate and acid sodium urate crystals 
should be washed, by decantation, several times with a small 
volume of 33 per cent, alcohol, and, after all of the soluble 
urinary salts have been removed, left in the last washing, 
and then placed in a clean, tightly stoppered bottle. 

Triple phosphate and acid calcium phosphate crystals should 
be washed, by decantation, several times with a small v oXmvcv^ 
of very dilute ammonic hydrate (i to 2 per cent.) ; finally 
they are left in the last washing, and placed in a clean, well- 
stoppered bottle. 

Some of these crystals, such as the oval and dumb-bell 
forms of calcium oxalate, cystin, triple phosphate, and acid 
calcium phosphate, frequently undergo partial solution in 
their respective media, particularly when kept in the bottle 
for several months or years. All crystalline sediments keep 
better when mounted on glass slides ; it is, therefore, advis- 
able to mount them as soon as possible after w^ashing. 

The washing can be done by the centrifugal or the 
gravity methods, the former having the advantage of com- 
pleting the washing in a i&ssi hours and before bacteria or 
other foreign substances enter the fluid. 

The Mounting of Urinary Sediments. — After the sedi- 
ments have been prepared in the manner described they 
can be mounted on glass slides, and thus preserved for 
years. 

Method. — Place a glass slide on a turn-table and make a 
cell by the use of Bell's cement and a camel's-hair brush. 
Allow the cement to dry thoroughly. Place a drop of the 
prepared sediment within the cell, and cover with a circular 
cover-glass of such a size that its margin rests well on the 
ring of cement. Take up the excess of fluid from around 
the cover-glass by means of a piece of filter-paper, care being 
taken not to admit air to the cell, and also to remove all air- 
bubbles that may be present. Return the slide to the turn- 
table, and carefully cover the margin of the cover with the 



MICRO-ORGANISMS. 265 

cement so as to make the cell air-tight. Allow this layer of 
cement to dr)% and in two or three days apply another coat. 
Mounts prepared in this manner will in most instances keep 
several years, and are very useful for purposes of demon- 
stration or for reference. 



MICRO-ORGANISMS. 

The micro-organisms that are found in the urine belong to 
the following different classes : Bacteria (nonpathogenic and 
pathogenic), molds, and yeasts, all of which properly belong 
to one general class called fungi. 

Fresh normal urine is free from bacteria or other micro- 
organisms, and, as has been repeatedly demonstrated, is a 
sterile fluid. Numerous investigations have shown that 
bacteria are usually, if not always, present in the urethra of 
both the male and female, particularly near the meatus ; 
therefore urine that was sterile intra vesicant becomes con- 
taminated as it passes through the urethra. 

Bacteria, being vegetable in their nature, belong to the 
class of fungi, and for purposes of study are more conven- 
iently divided into two classes : {a) nonpathogenic or those 
that are innocuous, and (B) pathogenic forms or those that 
are pyogenic in their nature. 

(a) Nonpathogenic Forms. — As already stated, fresh 
normal urine is free from bacteria, but when such urine is 
allowed to stand exposed to the air for some time, it soon 
becomes crowded with micro-organisms of various kinds, 
rendering the urine turbid and, for the most part, unfit for a 
satisfactory examination. 

The microscopic appearance of fermenting normal urine 
is subject to much variation. The conversion of urea into 
ammonium carbonate is probably effected through the 
agency of several forms of micro-organisms (Leube, C. 
Fliigge, V. Jaksch, v. Limbeck), of which the micrococcus 
urece (Fig. 47) is the most prominent, and at times may be 
seen in almost pure culture upon the surface of the decom- 
posing fluid. These micrococci form in long chain-like 
series, although they may occur as free, round, highly re- 
fracting dots ; they are usually of comparatively large size, 
and are constant inhabitants of the air. Of the other micro- 
organisms that have a part in the decomposition of urea, the 
staphylococcus urece candidus and stapJiylococcus urece lique- 



266 



URINARY SEDIMENTS. 



faciens (Lundstrom), bacillus iirece (Leube), tirobacillus 
Freiidenreichii, and the urobacilhis Maddoxii should also be 
mentioned. It is claimed that the urobacillus Maddoxii is 
the micro-organism that renders the urine viscid and 
stringy. A number of other bacteria have been isolated 
from decomposing urine, but little is yet known of their 
importance. Occasionally, long spiral bacilli with large 







Fig. 47.— Micrococcus ureae (after v. Jaksch). 

spores, and cocci that group themselves in globular masses 
of varying sizes are met with in the urine. 

Molds are, under normal circumstances, a very rare mani- 
festation in decomposing urine. In diabetic urine, however, 
they not infrequently make their appearance, especially after 
the alcoholic fermentation has ceased. They are then found 
floating in a layer on the surface of the urine. The urine 
is at the same time more or less turbid with bacteria and 
yeast fungi. 



^:"/ 




Fig. 48. — Sediment from fermenting diabetic urine with casts of micrococci : 
a, b, c, Various forms of uric acid ; rf, micrococci in form of casts; e, molds ;/", yeast 
fungi ; g, bacilli and micrococci (after v. Jaksch). 



The yeast fungus of the urine (saccharomyces urinae) 
consists, in the sporule stage, of transparent oval cells, which 
are seen both singly and in rows of two, three, or more. 
(Fig. 48, f.^ They are found in saccharine urine, and are 
identical with the yeast fungus (saccharomyces cerevisise). 
They grow in acid urine, but cease to multiply as soon as 
the urine becomes alkaline. 



MICRO-ORGANISMS. 267 

Yeast spores are distinguished from normal blood-corpus- 
cles by the fact that the former are smaller, perfectly color- 
less, and have usually a focal point. They differ from 
abnormal blood-corpuscles in having an oval shape, a focal 
point seen especially in the larger sporules, and a cell-body, 
the abnormal blood globule appearing simply as a ring 
— that is, apparently without a cell-body. (Compare p. 

233.) 

The presence of the yeast fungus in the urine is always 
suggestive of the presence of sugar, but in the experience 
of the writer this rule is by no means invariable. It occa- 
sionally happens that the urine to be examined has been 
placed in a bottle containing a mere trace of syrup ; in such 
a urine the yeast fungus grows rapidly. 

Penicillium glaucum is not infrequently met with in acid 
urine with or without sugar or albumin. The sporule stage 
furnishes cells very similar to those of the yeast fungus, 
but later the penicillium multiplies by linear division of 
cells, forming threads that have a characteristic appearance. 

The sarcina tirincB is a fungus only occasionally seen in 
the urine. It is smaller than that which forms in the 
stomach (sarcina ventriculi), being in point of size compar- 
able to the sarcina of the lung. They are cubes, each 
group of eight cells being so arranged as to resemble a 
** bale of goods." 

(b) Pathogenic Forms. — The pathogenic micro-organ- 
isms found in the urine may be divided into two classes — 
i. e.^ micrococci and bacilli. Of the micrococci the strepto- 
coccus pyogenes, the staphylococcus pyogenes albus, citreus, 
and aureus, and the gonococcus of Neisser are the most im- 
portant. The most common bacilli found in the urine are 
the bacillus coli comnmnis, the urobacillus liquefaciens septi- 
cus, and the tubercle bacillus. 

When recently voided urine is found to contain patho- 
genic micro-organisms, the condition becomes serious on 
account of the marked tendency to decomposition of the 
urine within the bladder. These micro-organisms occur in 
the freshly voided urine in connection with certain specific 
diseases, such as typhoid fever, erysipelas, relapsing fever, 
idcerative endocarditis, glanders, malignant pustule (bacillus 
of anthrax), septic processes, and tuberculosis. The spirilla 
of relapsing fever occur very rarely and only when hemor- 
rhage takes place in the kidney during an exacerbation (v. 



268 URINARY SEDIMENTS. 

Jaksch). According to Horton-Smith,^ the freshly voided 
urine of typhoid fever is usually turbid from the presence 
of the typhoid bacilli. Richardson ^ has recently shown 
that the virulence of these bacilli is destroyed by the inges- 
tion of urotropin (a formaldehyde compound). Actinomyces 
may also occur in the urine in instances in which the genito- 
urinary tract is infested with it, or in those cases in which 
it enters this tract from other parts (Braatz). Lustgar- 
ten and Mannaberg have found cocci in the urine in acute 
nephritis ; and Letzerich has found bacilli in the *' primary 
nephritis " of children. Mircoli also determined the pres- 
ence of pneumococci-like forms in the urine of children 
suffering from acute nephritis. Schweiger has demonstrated 
that in scarlet fever the urine is distinctly contagious ; and 
he claims that all renal lesions arising in the course of in- 
fectious fevers are caused by micro-organisms. 

In recent years the recognition of the tubercle bacillus in 
the urine or urinary sediment has been attended with great 
pathologic interest. A detailed consideration of this sub- 
ject, together with the method best adapted to the detec- 
tion of tubercle bacilli, will be found on page 325. It is of 
great importance to differentiate the tubercle bacillus from 
the smegma bacilhts, which is frequently present in the urine. 

Gonococci consist of diminutive kidney-shaped cocci 
aggregated in large groups. They are, for the most part, 
diplococci with the flattened surfaces of the kidney -shaped 
cocci presenting to each other. They are often found in 
abundance in the gonorrheal discharge from the urethra, 
within the pus-corpuscles and exfoliated epithelial cells, as 
well as free in the shreds of mucin. It has been satisfac- 
torily demonstrated that diplococci, in all respects resem- 
bling gonococci, exist in the genital tract. It is, therefore, 
exceedingly important from a diagnostic point of view to 
distinguish the gonococci from those that closely resem- 
ble them. This is best accomplished in the following way : 
First, stain a preparation with Loeffler's solution of methyl- 
ene-blue. If the characteristic groups of diplococci are 
found in the cells and pus-corpuscles, then stain a new 
preparation by Gram's method, as follows : (i) Cover the 
preparation with aniline-gentian-violet solution (without 

^ "Transactions of the Medical and Surgical Society," London. 
2 "The Journal of Experimental Medicine," vol. IV, No. I, 1899. 



PARASITES. 269 

heat) for thirty seconds ; (2) wash in water for two or three 
seconds; (3) cover the preparation with Gram's solution 
of iodine (iodine, i part ; potassium iodide, 2 parts ; water, 
250 parts) for thirty seconds ; (4) wash with 95 per cent, 
alcohol until the color ceases to come out of the prepara- 
tion ; (5) wash in water for two or three seconds ; (6) 
counterstain with saturated aqueous solution of Bismarck 
brown ten seconds ; (7) wash in water, mount, and examine. 
Gonococci are stained brown, while other diplococci are 
stained blue by this method. 

PARASITES, 

Filaria Sanguinis Hominis. — This is the parasite that 
causes the condition of cJiyliiria, This parasite was first dis- 




Fig. 49. — Eggs of distoma haematobium in sediment (after v. Jaksch). 

covered and described by Lewis, of Calcutta, who found 
them in large numbers in the urine and blood of persons 
who were passing milky or chylous urine. ^ 

Distoma Hceniatobiiim. — The eggs of this parasite are 
often found both in the urinary passages and in the urine 
of inhabitants of tropical climates. This worm infests the 
north and east coasts of Africa, and, according to Brock, is 
found also in South Africa. The eggs are oval, slender 
bodies, about o. 1 2 mm. long and 0.04 mm. broad, and fur- 
nished with a small spike, which projects from the ex- 

1 A detailed account of this parasite, together with an illustration of the 
same, will be found under the subject of Chyluria, p, 362. 



270 



URINARY SEDIMENTS. 



tremity or from the side. (Fig. 49.) Both the male and 
female parasites have been found in the branches of the 
portal vein, the splenic vein, the vesical plexus, etc., and 
are nourished by the blood. The male is from 1 2 to 14 mm. 
long, and the female is from 16 to 20 mm., and nearly 
cylindric in shape. (Fig. 50.) In case the individual is 
infested with this parasite the most prominent symptom is 




Fig. 50. — Distoma haematobium ; male and female, with eggs (after v. Jaksch). 

severe burning pain during micturition. The pain is usu- 
ally momentary, and caused by the passage of the Gggs 
along the urethra, which they irritate by their sharp angles. 
The urine usually contains blood- and pus-corpuscles, with 
eggs of the parasite, and sometimes a considerable quantity 
of fat. There are often marked cystitis, pyelitis, sometimes 
nephritis, and septic processes. 

Echinococci. — Echinococcus cysts have been found in 







Fig. 51. — Echinococcus scolices and hooklets (after Heller). 



the kidney, although rarely. Usually, only one kidney is 
affected. The hydatid growth is made up of an outer cap- 
sule, within which the mother cysts are found. Within 
the mother cysts are the daughter cysts. Both the large 
mother cysts and the smaller daughter cysts float freely in 
the liquid contents of the capsules holding them. This 
peculiar growth is caused by a very small tapeworm, — the 



PARASITES. 



271 



sM 



tcvnia cchinococais, — whose natural size is about that of a 
millet seed. (Fig. 52.) This worm consists of a head 
much like that of the ordinary tapeworm, four mouths or 
suckers, and a double row of hooklets. 

The scolices and hooklets (Fig. 51) occasionally find their 
way into the urine, either from the cysts in the kidney or 
from some neighboring organ, as the result of rupture. The 
hooklets are usually accompanied by 
more or less blood, leucocytes, and at 
times shreds of membrane forming the 
hydatid cyst. The diagnosis of echino- 
coccus growth of the kidney is only 
made with certainty by finding charac- 
teristic hooklets in the urinary sediment. 

Hydatid disease of the kidney in man 
is most commonly contracted from the 
doer, whose intestinal tract is often in- 
fested with large numbers of echinococci. 
The eggs that are passed with the stools 
find their way into the food, thence to 
the stomach of man ; as the embryo 
hatches it enters the blood, is carried to 
the liver or kidneys, where it forms the 
hydatid cyst. This disease is most com- 
mon in the arctic regions, where the 
natives live with their dogs, and it is 
said that in Iceland approximately one- 
seventh of the mortality is due to hydatid 
disease. 

Eiistroiigyhis Gigas. — -The presence of 
this parasite in the urine is a very rare oc- 
currence. According to the researches 
of Leuckart,^ the existence of this para- 
site in man is a matter of some doubt. 

Ascarides. — In rare instances ascarides 
-have been found in the urinary passages, 
in the urine is usually explained by an abnormal communi- 
cation between the intestine and the urinary tract. Scheiber ^ 
reports having found in the urine of a woman worms that he 
considered had been derived from the genital organs, and he 
has named them rJiabditis genitalis. 

1 Leuckart, *' Deutsche med. Wochenschr.," XIII, S. 390. 

2 Scheiber, " Virchow's Archiv," Lxxxn, 161, 1884. 



Fig. 52.— Taenia 
echinococcus, enlarg- 
ed. Above, at the 
right, echinococcus 
of natural size (after 
Heller). 



Their presence 



CHAPTER VII. 

URINARY CONCRETIONS. 

Urinary concretions or calculi consist of an aggregation 
of solid matter that has become separated or precipitated 
from the urine. They may form in any part of the urinary 
tract, from the tubules of the kidney to the meatus urina- 
rius. They vary very much in their composition, but in- 
variably consist of certain constituents of the urine — either 
normal or pathologic — that have separated or become pre- 
cipitated from it. The nucleus may, however, consist of a 
foreign body that has been introduced into the urinary pas- 
sages, or of certain substances that have their nativity in 
the body, such as mucous or blood coagula, or fragments 
of morbid tissue that have become detached. Of the for- 
eign substances that have been found to form the nucleus 
of urinary calculi may be micntioned peas or beans that 
have been introduced into the urethra by the insane or by 
children, pieces of catheters or bougies that have been acci- 
dentally broken off in the urethra or bladder, pieces of soap 
or candles, hairpins, pins, needles, and bullets that have 
lodged in some portion of the urinary tract. From this 
it is seen that the nucleus of a urinary calculus may be any 
substance that has its origin in the body and that exists in 
solid form in the urinary passages, or a foreign body that 
may have been accidentally or intentionally introduced into 
them. 

The conditions of the urine favoring the growth of calculi 
are variable. Among the causes may be mentioned (i) a 
diminution in the amount of water excreted ; (2) a change 
in the reaction of the urine, whether abnormally acid or 
alkaline ; (3) an increased formation of some of the less 
easily soluble constituents of the urine. Changes in the 



URINARY CONCRETIONS. 273 

reaction embrace hyperacidity, which favors the deposition 
of uric acid and urates and of calcium oxalate by diminish- 
ing; the solvent action of the urine over these substances ; 
and an alkaline condition of the urine, which causes the 
separation of the phosphates and carbonates of calcium 
and magnesium and of ammonium urate. The chief effect 
of an increased acidity of the urine is to lessen the solu- 
bility of the uric acid by diminishing the amount of alkali 
with w^iich it may enter into combination. Uric acid is 
usually present in the urine in solution in the form of nor- 
mal urate of sodium or potassium, which is very soluble in 
water. In case the uric acid is deprived of a part or the 
whole of its base, either the acid urate of potassium or 
sodium or uric acid is the result. These substances, being 
much less soluble in water than the normal urates, separate 
from the urine, and tend to become aggregated in the form 
of concretions. An alkaline reaction of the urine may be 
due to the presence of either a fixed alkali or to free am- 
monia and ammonium carbonate. It rarely happens that a 
calculus forms as a result of a deposition of the earthy 
phosphates by a fixed alkali, as is well demonstrated in 
those cases in which alkaline remedies are given for a long 
time, as in the treatment of acute rheumatism, and also in 
those cases in which the urine is habitually alkaline, as in 
some cases of faulty metabolism. 

Of much greater importance is an ammoniacal reaction 
that frequently results in a calculus formation by the de- 
position of triple phosphate, amorphous phosphates, and 
ammonium urate. (See Reaction, p. 3 i.) Concretions from 
this cause are quite commonly met with in cases of irritation 
or inflammation of the bladder, the change from a normally 
acid to an alkaline reaction being due to the presence of the 
urea ferment that decomposes the urea. A deposit of phos- 
phates always tends to increase the size of any calculi that 
may already exist. 

~ A diminution in the amount of water excreted, particu- 
larly when coupled with an increased formation of any of 
the sHghtly soluble constituents of the urine, such as uric 
acid and acid urates, calcium oxalate, cystin, and very rarely 
xanthin, favors the tendency to the formation of concretions 
within the urinary passages, since these substances do not 
find a sufficient amount of urine to hold them in solution. 



274 URINARY SEDIMENTS 



CONSTITUENTS OF URINARY CALCULI. 

These are either organic or inorganic or a mixture of 
the two. They are conveniently divided into two classes, 
as follows : (i) PTunary constituents, or those which sepa- 
rate from the urine without any material change in the 
character of the urine, other than changes referable to 
altered metabolism ; and (2) secondary constitiieiits, or those 
which separate from the urine as a result of ammoniacal 
fermentation. 



Primary Cotistituetits. 


Seco7idary Constituents. 


1 sodium. 




I ammonium. 




Uric acid and urates of ( potassium. 


Calcium phosphate. 


/ calcium. 




\ magnesium. 




Calcium oxalate. 


Calcium carbonate. 


Calcium phosphate, both crystalline 


Ammonio-magnesium phosphate 


and amorphous. 


(triple phosphate). 


Calcium carbonate. 


Ammonium urate. 


Cystin. 




Xanthin. 




Indigo. 




Urostealith (Heller). 




Silica. 




Albuminous substances (blood, pus. 




etc.). 




Bilirubin (hematoidin). 





Urate of ammonium, calcic carbonate, and calcic phos- 
phate may, therefore, be either primary or secondary con- 
stituents. 

Urinary concretions are most commonly found in the 
pelvis of the kidney and in the bladder, but they may form 
in any part of the urinary tract. In the Warren Museum 
at the Harvard Medical School is a rare specimen showing 
a number of medium-sized concretions in the pelves of both 
kidneys and in both ureters, also a large calculus in the 
bladder. Calculi are also sometimes formed in sinuses con- 
necting the urinary passages with the intestines, uterus, or 
vagina. 

The mnnber of concretions that may be present in the 
urinary passages is almost unlimited ; often there is only a 
single stone, but there may be several hundreds. 

Urinary concretions vary in size from that of a pinhead 
to that of an orange or even larger. Those of small size 



CONSTITUENTS OF URINARY CALCULI. 275 

have been somewhat arbitrarily termed sand or gravel, 
while those of large size are called stones or calculi. The 
size of a calculus is limited only by the dimension of the 
cavity in which it is formed. The smaller concretions 
usually emanate from the kidney or pelvis of the kidney, 
while those of large size generally come from the bladder. 
Concretions vary in weight from a few milligrams to several 
grams ; in the Dupuytren Museum, at Paris, is a calculus 
weighing 1596 grams. 

The surface of a urinary calculus varies with its composi- 
tion and its location in the urinary tract. Those consisting 
of uric acid, phosphates, and cystin are usually smooth, 
while those made up of calcium oxalate are generally 
rough and lobulated — nudberry calculi. In case several 
concretions occupy a single cavity — for example, the 
bladder — their surfaces are often polished in those portions 
that rub against each other during the natural movements 
of the bladder wall or during the changes in position of the 
body. The smooth or polished surfaces are termed facets. 

The shape of urinary calculi varies as the location. Those 
in the kidney proper are generally very irregular ; they 
often have small projections that have extended into cavities 
formed by the destruction of the renal tissue. Calculi in 
the pelvis of the kidney when large usually assume the 
form of that cavity, projections taking place into the calices, 
and giving the calculus in some cases a shape not unlike 
that of an elephant ; small concretions in the pelvis are 
generally round or oval. Calculi in the bladder vary 
greatly in shape. If only a single concretion be present, it 
is usually round, oval, or sometimes flat. If numerous 
calculi are present, their form may be modified by constant 
pressure against each other. Occasionally, a calculus 
becomes partially encysted in the bladder, so that the 
deposit takes place only upon one portion, thereby causing 
the growth of the calculus to take place in one direction 
only, and giving it a very irregular shape. Those that 
have forrhed in the urethra are generally oblong or cylindric 
in shape, and when there are several, the ends of those that 
are adjacent are often highly polished. 

The color of calculi varies with their composition and the 
admixture of organic subtsances such as blood, pus, fibrin, 
etc. Those consisting of uric acid and urates are always 
colored, varying between a pale straw and a dark brown, 



276 URINARY SEDIMENTS. 

the coloring-matter being derived chiefly from the urine. 
Calcuh consisting of calcium oxalate are often of a dark- 
brown color due chiefly to the presence of decomposed 
blood and of fibrin. Phosphatic calculi are generally gray- 
ish or white, while those made up of cystin are usually yellow 
in color. 

The composition of urinar^^ calculi may be simple, con- 
sisting of only one constituent of the urine, such as uric 
acid or calcium oxalate, or it may be compound, with two 
or more primary deposits occurring in separate and alternate 
layers, the most common of these constituents being uric 
acid and calcium oxalate. Several of the constituents may 
be mixed in any portion of the stone. It is not uncommon 
to find a calculus with a central portion composed of alter- 
nate layers of two or more of the primary constituents and 
an outer layer of some one of the secondary constituents. 

Most urinary calculi consist of three distinct parts — /. c, 
the nucleus ; the body ; and the crust. The imdetis occu- 
pies the center and may have the same composition as the 
rest of the concretion, but it often consists of some albu- 
minous body, such as a coagulum of fibrin, or mucus or 
pus mixed with uric acid, urate, or calcium oxalate crystals 
about which are deposited other similar or perhaps entirely 
different urinary constituents. A concretion may have 
several nuclei, as, for example, when two or more small 
calculi become united to form a single stone ; these nuclei 
are readily seen when a section is made through the calcu- 
lus. The nucleus varies much in size and usually occupies 
the center of the concretion, but it may be excentrically 
placed especially if the growth of the calculus is only in 
one direction. 

The body comprises the greater part of the calculus and 
surrounds the nucleus ; it may or may not have the same 
composition as the nucleus. The body may consist of 
concentric layers of two or more urinary constituents, such 
as a layer of uric acid and urates, another of calcium oxa- 
late, and so on for several layers. The several layers of the 
body may be differently colored ; even those having the 
same composition may be variously colored. 

The crust or external envelop of the calculus is deposited 
upon the body, and always consists of one or more of the 
secondary constituents of the urine, the phosphates usually 
predominating ; in other words, the crust is always found 



URIC ACID AND URATE CONCRETIONS. 277 

after ammoniacal fermentation of the urine has taken place, 
and it usually forms upon vesical calculi. Concretions that 
ha\'e formed in an acid urine do not, therefore, have a crust. 
Calculi that have smooth surfaces like the uric acid and 
urate may not have a crust formation even when present in 
an ammoniacal urine, but calculi consisting of calcium oxa- 
late, on account of their rough surfaces, usually have a crust 
formation and sometimes the deposit begins while they are 
quite small. As a rule, the time required for the beginning 
of formation of a crust depends largely upon the time nec- 
essary for the calculus to produce a cystitis. 



URIC ACID AND URATE CONCRETIONS. 

Calculi consisting partly or entirely of uric acid and 
urates comprise the great majority of concretions found 
in the urinary tract. They are very common as renal 
calculi in children, especially those consisting chiefly of 
ammonium urate. They are generally smooth, oval, or 
round and of a yellow or brown color. When such con- 
cretions are formed in the kidney or pelvis of the kidney, 
they may be washed out with the urine singly or in num- 
bers, and are then found to vary in size from a pinhead to 
that of a kernel of wheat, or to that of a pea. Their pas- 
sage down the ureter is accompanied by more or less pain, 
so acute at times as to cause the symptoms of renal colic. 
If these small concretions are retained in the bladder, they 
usually grow more or less rapidly, and then instead of being 
perfectly smooth are often irregular, and vary in weight from 
a few grains to several ounces. When uric acid and urate 
concretions are forming, the urine is usually found to be 
concentrated, highly colored, of strongly acid reaction, and 
of high specific gravity. The sediment generally contains 
crystals of uric acid or the hedgehog forms of acid ammo- 
nium urate, or the stellate groups of sodium urate ; there is 
usually also evidence of more or less irritation of the kid- 
neys and frequently signs of mechanical irritation of the 
bladder that has been set up by the crystalline elements. 

Concretions that consist chiefly of urates do not usually 
attain the large size of the mixed uric acid and urate calculi, 
rarely being found larger than an average sized marble. 
They are usually lighter in color and not so hard as the 



278 URINARY SEDIMENTS. 

mixed concretions. When some of the powdered calculus 
is heated on platinum foil, it chars and completely disap- 
pears if uric acid or ammonium urate be the only constituent ; 
but if sodium urate be present, there remains a residue that 
•is soluble in water and has an alkaline reaction (carbonate 
of the alkali). 



CALCIUM OXALATE CONCRETIONS, 

These are met with most often as medium or large, dark 
brown, rough, trabeculated bodies having a mulberry-like 
surface, hence the name " mulberry calculi y They are very 
hard and can be crushed only with difficulty. Calcium oxa- 
late concretions are composed chiefly of calcium oxalate 
which is mixed with more or less organic matter. Occasion- 
ally the body of the calculus consists of alternating layers 
of calcium oxalate and uric acid. The nucleus often consists 
of uric acid and urates, or a coagulum of blood or mucus ; 
it may, however, be made up entirely of calcium oxalate. 
As previously stated, calcium oxalate concretions are very 
apt to have a crust consisting chiefly of phosphates. 

The characteristics of the urine from which oxalate con- 
cretions are being deposited are very much the same as 
when uric acid and urate concretions are forming. The 
sediment will contain crystals of calcium oxalate and evi- 
dences of a more or less marked irritation of the kidneys 
and bladder. If the stone is forming in the bladder, a 
typical chronic cystitis may exist. When some of the pow- 
dered calculus is heated on platinum foil, it chars slightly, 
on account of the organic matter that is mixed with it ; there 
remains a white residue of calcium oxide or calcium car- 
bonate, according to the amount of heat used. If the 
former, it will be found to be only slightly soluble in a 
drop of water, which will have an alkaline reaction ; if the 
latter, it will dissolve with effervescence in a drop of acetic 
acid. 



PHOSPHATIC CONCRETIONS. 

These always form in neutral or alkaline (ammoniacal) 
urine and originate chiefly in the bladder. They are usually 



CALCIUM CARBONATE CONCRETIONS. 279 

Avhite or of a grayish color, quite soft and easily crushed. 
They are often covered on their surface with bright, glisten- 
ing points representing large crystals of triple phosphate. 
The surface may be smooth or rough ; if it is smooth it 
frequently has the feeling of chalk. Phosphatic concre- 
tions having a grayish color are usually harder than the 
white or chalky calculi. The former consist chiefly of cal- 
cium phosphate, while the latter are composed chiefly of 
triple phosphate. Concretions that consist solely of cal- 
cium phosphate, or triple phosphate are very uncommon, the 
mixed phosphatic calculus being the one met with most fre- 
quently. 

If some of the powdered calculus be heated on platinum 
foil it does not char or burn, but a bulky residue remains 
which dissolves in acetic acid without effervescence, as does 
the original powder. 



CALCIUM CARBONATE CONCRETIONS. 

Concretions composed of calcium carbonate are very rare 
in man, very few cases having been reported. They are not 
uncommon in the herbivora. They are usually small, of a 
grayish color, of smooth surface and very hard. Calcium 
carbonate concretions are generally spherical in shape, and 
on section they present concentric lines. When some of 
the original powder is treated with a drop of acetic acid it 
dissolves with effervescence ; when the powder is heated on 
platinum foil to a white heat it is converted into calcium 
oxide, which is but slightly soluble in a drop of water, the 
solution having an alkaline reaction. 



CYSTIN CONCRETIONS. 

These are among the rarer forms of calculi. They are 
quite soft and of a pale-yellow color. As a rule, they are 
oval or cylindric in shape with a rough — finely granular — 
surface. They may form in the kidneys or bladder, the 
latter location being perhaps the more common. 

Cystin calculi when taken from the body usually have a 
yellow color not unlike beeswax, but after being exposed 



280 URINARY SEDIMENTS. 

to the light for a long period the color changes to a green. 
They are generally of light weight and vary much in size. 

Probably the largest cystin calculus in existence is the 
one reported by Dr. E. S. Wood. ^ It was removed from 
the bladder by Dr. J. C. Warren, and weighed, after drying, 
101.883 grams. It was in the form of a flattened oval, and 
measured 2 5^ X 2 ^^ X i ^ inches. 

Upon section they are found to be crystalhne and present 
a radiating appearance. When some of the powdered cal- 
culus is heated on platinum foil it burns with a blue flame, 
and the odor of burning sulphur is evolved ; no residue 
remains after ignition. Cystin is recognized by its solubility 
in alkaline hydrates and in strong acids, also by its insolu- 
bility in acetic acid. If some of the powder be treated with 
a drop of ammonic hydrate on a glass slide, it will dissolve ; 
and if the mixture be allowed to stand until the ammonia 
has escaped, the residue will be found to consist of the 
colorless hexagonal cr>^stals of cystin. 



XANTHIN CONCRETIONS. 

These are very rare, being probably the rarest of all of 
the urinary calculi. They may consist entirely of xanthin, 
or the xanthin may be mixed with uric acid and urates. 
The cases of xanthin calculi thus far reported have occurred 
in children. Xanthin concretions vaiy in color from a white 
or pale yellow to a brown, and they range in size from a 
bean to a hen's egg. 

When some of the powdered calculus is heated on plati- 
num foil, it chars and entirely disappears ; in this respect it 
resembles uric acid. But xanthin can readily be distin- 
guished from uric acid by a modification of the murexide 
test (see p. 66). If some of the powdered calculus be 
treated with a drop of nitric acid on a porcelain surface 
and evaporated to dryness, and the residue treated with a 
drop of potassic hydrate, a pinkish tint appears which, if 
xanthin be present, deepens to a violet on warming. Uric 
acid gives a violet with potassic hydrate, the color disap- 
pearing on warming. 

1 " Journ. Boston Soc. Med. Sciences," Feb., 1898, p. 82. 



INDIGO CONCRETIONS. 281 



INDIGO CONCRETIONS. 

These are also exceedingly rare. Ord ^ has reported a 
case in which an indigo calculus was found in the pelvis of 
the right kidney of a woman whose left kidney was de- 
stroyed by sarcoma. The stone weighed 40 grams, and 
had a nucleus consisting of a coagulum of blood and a 
deposit of calcium phosphate. Indigo derived from a de- 
composition of the indican of the urine was deposited upon 
one side of the calculus. Forbes ^ has also reported an 
indigo calculus which was found in the pelvis and a calyx 
of one kidney. The stone weighed 147 grains ; its greatest 
thickness, fore and aft, was -|-|- of an inch ; it measured 
across its base i ys inches, and from base to apex i ^ inches. 
It w^as dark brown in color ; and when it was drawn across 
white paper, it left a rough, blue mark. The specimen can 
be seen in the Museum of Jefferson Medical College, Phila- 
delphia. 

So far as the author is aware these two cases of indigo 
calculus are the only ones that have thus far been recorded. 



UROSTEALITH CONCRETIONS. 

Urostealith, or fatty concretions, are very rare. They are 
soft and elastic when fresh ; but when dry they are hard 
and brittle. They are generally of a yellowish or brown- 
ish color, and are frequently enclosed within a phosphatic 
crust. When some of the calculus is heated on platinum 
foil it burns with a yellow flame and gives off an odor not 
unlike that of benzoin or shellac. 



FIBRIN OR BLOOD CONCRETIONS. 

. These are formed as a result of the coagulation of blood 
in the urinary tract. They are commonly found as nuclei 
of other calculus growths, and not infrequently contain a 
deposit of uric acid, calcium oxalate, or phosphates. When 



^ Ord, "Influence of Colloids upon Crystalline Form and Cohesion in 
Urinary and Other Calculi," London, 1879, p. 144. 

2 "Medical News," Aug. 18, 1894. 



282 URINARY SEDIMENTS. 

portions of calculi containing a large proportion of organic 
matter are heated on platinum foil, they give off the odor 
of burnt horn and burn with a yellow flame. 

Concretions containing crystals of hematoidin are occa- 
sionally seen. These crystals are most commonly seen in 
fibrin concretions, or in those calculi that have formed in 
the presence of a considerable amount of blood. 



PROSTATIC CONCRETIONS. 

Concretions emanating from the folhcles of the prostate 
are occasionally discharged with the urine. They usually 
have a laminated nucleus consisting of amyloid bodies (cor- 
pora amylaced) about which is deposited a mixture of 
ammonio-magnesium phosphate and calcium phosphate. 
They do not, as a rule, produce symptoms until they have 
attained a large size ; prostatic concretions of large size are, 
however, rare. 



CHEMIC EXAMINATION OF URINARY CALCULI. 

Before beginning the chemic examination of a calculus, 
its size, shape, color, and density should be observed, as 
these properties often suggest the probable composition of 
the concretion. Since a calculus may consist of alternate 
layers of two or more substances, it is first necessary to 
make a section through the center of the stone by saw- 
ing, in order to determine the composition of each layer. 
If several different strata are found, it is essential that 
a portion of each la}'er be subjected to chemic exam- 
ination ; that portion to be tested should always be in 
the form of a fine powder, which can be obtained by scraping 
a very small amount of the stone from its cut surface by 
means of a knife-blade, or by placing small particles of the 
calculus in a mortar and grinding them to a powder with a 
pestle. If the section of the stone is found to have a 
homogeneous appearance, it is only necessary to examine 
the sawdust ; it is, however, advisable to make a separate 
examination of the nucleus in every instance, since this por- 
tion of a concretion is subject to marked variation. 

The chemic examination is best conducted in the follow- 
ing manner : 



CHEMIC EXAMINATION OF URINARY CALCULI. 283 

Preliminary Examination. — Heat on platinum foil : 

Albumin = a flame with odor of burnt horn. 

Urostealith = a flame with odor of shellac and benzoin. 

Cystm = a blue flame with odor of SOg. 

Xanthin and uric acid =^ char without a flame. 

Alkaline urates = alkaline residue soluble in H^O. 

Earthy phosphates = a residue soluble in acetic acid with- 
out effervescence. 

Calcium oxalate and calcium carbonate =^ a residue soluble 
in acetic acid with efl'ervescence. 

Calcium carbonate = original powder soluble in acetic 
acid 7£jith effervescence. 

Calcium oxalate =^ onginal powder insoluble in acetic acid. 

Silica = residue insoluble in HCl. 

Murexide Test for Uric Acid. — Original powder -(- HNO3 
and evaporate = pink residue -j- NH^OH = purple 
color = uric acids and urates. 

Original powder + HNO3 and evaporate -f KOH 
=^ violet color, which disappears on heating = uric 
acid. Violet increases on heating = xanthin. 
Systematic Examination. — Presence of uric acid 
shown by (i). Boil in H^O and filter. 

A. Filtrate 4- HCl. Let stand 24° = crystals of uric 

acid. Bases in solution. Concentrate. 

Calcium urate = one drop of solution + solution ammo- 
nium oxalate = crystals calcium oxalate. 

Magnesiwn urate = one drop of solution -\- NH^OH -f 
Na^HPO^ =^ crystals ammonio-magnesium phosphate. 

Sodium w-ate = one drop of solution -f Pt.Cl^ = after 
concentrating, prisms of sodioplatinic chloride. 

Potassium urate and ammonium urate = one drop of solu- 
tion -|- Pt.Cl^ = dodecahedra of potassioplatinic 
chloride and ammonioplatinic chloride. 

Potassium Urate. — Evaporate solution and igniteon mica. 
Residue -f- HCl -{- Pt. 01^= potassioplatinic chloride. 

Ammonium Urate. — Evaporate solution and ignite on 
mica. Residue = no crystals with Pt.Cl^. 

B. Portion insoluble in H^O. Add HCl. 
Uric acid = insoluble. 

Calcium carbonate = soluble with effervescence. Filter -f- 
NH^OH = precipitate of calcium oxalate, calcium 
phosphate, and ammonio-magnesium phosphate. 
Wash. Calcium oxalate = insoluble in acetic acid. 
Filter + ammonium oxalate to filtrate. Calcium 
phosphate gives precipitate of calcium oxalate. Fil- 
ter -j- NH^OH to filtrate =; precipitate of ammonio- 
magnesium phosphate. 



PART II. 
DIAGNOSIS 



CHAPTER VIII. 

DISTURBANCES AND DISEASES OF THE 
KIDNEYS. 

ACTIVE HYPEREMIA. 

Active hyperemia — active congestion — is essentially 7iot 
a disease of the kidneys, but a disturbance of the functions 
of these organs. This condition is invariably due to the 
presence of some irritant that is within or is passing through 
the kidneys, or to some alteration in their circulation — in 
other words, it is always secondary in its nature. 

Causes. — The causes of active hyperemia may be divided 
into three general classes : 

I. Any general disease or disturbance, -which is not 
primarily renal, but which may cause a change in the 
renal circulation, as in severe nervous diseases, notably 
delirium tremens and acute mania ; also in other serious 
affections that act by causing a change in the pressure of 
the blood in the renal vessels. 

Exposw^e to cold and wet may set up an active hyperemia 
of the kidneys or an acute nephritis. The reason for a 
renal disturbance under such circumstances probably is that 
the superficial blood-vessels and the capillaries of the skin 
suddenly contract, due to vasomotor changes, congesting 
the internal organs, and, since the function of the skin is 
interfered with, the renal congestion is augmented by the 
necessity for increased activity of the kidneys. 

II. Irritants Within or Passing Through the Kid- 
neys. — These may be divided into two distinct classes — 
viz., insoluble and soluble. 

2>^4 



ACTIVE HYPEREMIA. 285 

(a) Insoluble Irritants. — These are crystalline substances 
that may be separated from the urine in the kidneys, and 
may set up a mechanical disturbance in the renal tubules — 
e. g., uric acid, acid ammonium or sodium urate, calcium 
oxalate, acid calcium phosphate, and cystin. 

(b) Soluble Irritants. — Of these there are — 

1. The toxines, which are soluble poisons formed and 
eliminated during the progress of disease. Their irritating 
effect is especially seen in the acute diseases — viz., pneu- 
monia, typhoid fever, erysipelas, measles, scarlet fever, diph- 
theria, acute rheumatism, acute miliary tuberculosis, cere- 
brospinal meningitis, malaria, etc.; and not infrequently in 
chronic diseases, such as pulmonary tuberculosis, chronic 
rheumatism, chronic malaria, etc. Irritant toxines may also 
be formed in the intestines as a result of faulty processes 
going on there. These are absorbed by the blood and 
eliminated by the kidneys, causing an active hyperemia. 
This is especially seen in children who are suffering from 
diarrhea or an enterocolitis. 

Toxines may also be formed in those acute and chronic 
local diseases that are attended with suppuration, notably 
urethritis, prostatitis, vesiculitis, bone diseases, abscesses 
(from which there is absorption), and diseases of the female 
genitalia, the disturbing element being a toxine that is ab- 
sorbed from the seat of the disease by the blood and elimi- 
nated by the kidneys. 

2. Drugs. — The elimination of any irritating drug, such 
as arsenic, lead, mercury, cantharides, salicylic acid, po- 
tassium chlorate, phenol and its compounds, volatile oils, 
etc. 

J. Concentrated Urine. — Not infrequently the passage of 
a concentrated urine sets up an active hyperemia that varies 
in intensity from a very mild condition to one that is quite 
severe. It is especially seen if the urine has been in a state 
of concentration for a long time. An active hyperemia 
from this cause rapidly disappears when the patient is given 
plenty of diluent drinks, the urine becoming diluted and 
less irritating. 

^. Bile. — This substance acts as an irritant in its way 
through the kidney. It is obvious that the merest trace of 
bile would not, as a rule, produce any active hyperemia, 
whereas larger amounts generally set up a more marked 
form of this disturbance. 



286 DISTURBANCES AND DISEASES OF THE KIDNEYS. 

5. Sugar. — What has been said of bile may also be 
credited to sugar. The author has yet to see a urine con- 
taining bile or sugar — especially if one or the other were 
present for more than a day or two and in more than the 
slightest trace — where there was not evidence of an irrita- 
tion of the kidneys. ■ 

III. Irritants Extending Upward from the Lower 
Urinary Tract. — It is not uncommon to have a gonorrheal 
inflammation extend upward from the urethra and bladder, 
and involve the straight or collecting tubules of the kidney. 
The same danger exists in an inflammation of the bladder 
from any other cause. 

In case there is some obstruction to the outflow of urine, 
as by a urethral stricture or an enlarged prostate, the col- 
lecting tubules may dilate, and finally result in a *' surgical 
kidney." 

Various bacteria, more especially tubercle bacilli, whether 
coming from the lower urinary passages by extension or 
by way of the blood-vessels, may set up a focal active 
hyperemia of the kidneys. The disturbance is principally 
confined to the pyramidal portion with more or less evi- 
dence of extension into the cortical portion of the kidney. 
Reference will again be made to this under the heading of 
Tuberculosis of the Kidney. 

Character of the Urine. — This varies as the cause : 
e. g., if the hyperemia is due to the elimination of toxines 
that are produced in the course of an acute febrile dis- 
ease, we will generally find a highly colored, concentrated 
urine, whereas if the cause of the irritation is not accom- 
panied by fever, the urine may have about a normal con- 
centration, or it may be dilute. 

It is, of course, impossible to give the characteristics of 
the urine that will apply in every case of active hyperemia, 
yet a few general rules may be laid down concerning the 
average urine in this disturbance. 

Quantity in Twenty-four Hours. — Usually less than 
1500 c.c. ; average, from 800 to 1200 c.c. It may be as 
low as 300 or 400 c.c, and may exceed 1500 c.c, but only 
for a short time. 

Color. — Normal or high. Not infrequently it is paler 
than normal. It may be slightly smoky (usually seen, 
however, in severe active hyperemia, or catarrhal nephritis). 
(See p. 288.) 



ACTIVE HYPEREMIA. 287 

Reaction. — Almost always acid, and frequently strongly 
acid. 

Specific Gravity. — This varies according to the metab- 
olism and quantity of urine ; it is generally normal or high 
(1018 to 1030), sometimes less than normal. It usually 
bears an inverse relation to the quantity of urine passed — 
€. g., quantity of urine in twenty-four hours 800 c.c, spe- 
cific gravity 1030; or quantity 2000 c.c, specific gravity 
10 1 4. This, however, is not always the case, for both the 
quantity and specific gravity may be below the normal at the 
same time — ^.^., quantity 1200 c.c, specific gravity 1012. 

Normal Solids (Urea, Uric Acid, Chlorides, Phosphates, 
and Sulphates). — Absolutely, about normal or slightly di- 
minished, depending upon the metabolism. In case the 
metabolism is much reduced, as by an acute infectious dis- 
ease, the solids may be found, absolutely, very much dimin- 
ished. In diabetes mellitus they are usually absolutely 
increased. They are relatively increased if the urine is 
concentrated ; and relatively diminished if the twenty-four- 
hour quantity is near the normal and the metabolism is low. 

Albumin. — The quantity varies as the cause and the 
severity. If the irritation is slight, there may not be more 
than the slightest possible trace or a slight trace. On the 
other hand, if the hyperemia is severe, as following expo- 
sure to cold and wet, the quantity of albumin may go as 
high as ^ of I per cent., but such an amount rarely con- 
tinues for more than a day or two, when it will fall to a trace, 
slight trace, or even the slightest possible trace. (See Severe 
Active Hyperemia.) Very soon after the removal of the 
cause of the irritation the albumin entirely disappears, but 
not until all of the renal epithelium that has been denuded 
by the irritant or other active process has been restored to 
the tubules. 

Sediment. — Usually considerable in quantity, and in the 
average mild case consists of an occasional (or few) hyaline 
and finely granular cast, with blood and renal cells adherent. 
An occasional (or few) free renal cell and blood globule. 

If crystalline elements, such as uric acid or calcium 
oxalate, are the cause of the disturbance, they will generally 
be found in the sediment, and occasionally embedded in the 
casts. Normal blood also is very apt to be found under 
these circumstances, as a result of the mechanical irritation 
by the crystals. 



288 DISTURBANCES AND DISEASES OF THE KIDNEYS. 

Long- continued Active Hyperemia. — If the source of 
irritation has not been removed, and the hyperemia con- 
tinues for months or years, fatty elements, such as fatty renal 
cells, fat drops adherent to the casts, compound granule cells, 
and rarely a small fatty cast, may be found in the sediment. 
These fatty changes evidently result from the interference 
with the nutrition of the renal epithelium. Besides the fatty 
elements there is not infrequently a little more abnormal 
blood than in the average mild hyperemia of short duration. 

The solids will usually be found to be absolutely more 
diminished than in the average temporary irritation. 

Severe Active Hyperemia (" Catarrhal Nephritis"). — 
A mild active hyperemia may gradually or suddenly become 
intensified, especially during the progress of acute infectious 
diseases, and a mild but true inflammatory process exist. 
A severe irritation of the kidneys may, however, be severe 
from the start, as is sometimes seen in cases of exposure ta 
cold and wet. 

Causes. — Any of the causes of an active hyperemia 
already enumerated may result in a severe renal congestion ; 
toxines are especially liable to produce this condition. 

Character of the Urine in the Acute Stage. 

Quantity. — Usually below the normal — 600 to 1000 c.c. 

Color. — Smoky, because of the altered blood pigment 
(methemoglobin or hematin). If there is very much nor- 
mal blood present, the urine may have a blood-red color. 

Reaction. — Generally strongly acid. It may, however, 
have the normal acidity. 

Specific Gravity. — This varies from 1018 to 1025 — in 
other words, not far from the normal. Of course, if the 
metabolism is much diminished, it may be as low as 1012 
to 1015. 

Solids. — Absohde. — The absolute solids are usually some- 
what below the normal, but dependent upon the metabolism. 
In pneumonia they may be high during the first few days 
of the acute stage, but later on they may be very low, when 
not only the metabolism is low, but there is a serous exuda- 
tion or effusion, into which to a greater or less extent the 
chlorides and urea go. Relative. — As a rule, the relative 
solids are about normal. They may be a little high or even 
below normal, depending upon the degree of concentration 
of the urine. 

Alhunin. — This varies in quantity from a slight trace to 



ACTIVE HYPEREMIA. 289 

J/^ of I per cent. The large quantity of albumin, however, 
is usually present only for a short period (a day or two), 
and then falls to about a trace. The comparatively small 
quantity of albumin (slight trace or trace) is one of the 
important elements in the diagnosis of a catarrhal nephritis 
as distinguished from an acute nephritis, which is character- 
ized by a large amount of albumin ( j{ to i ^ per cent.). 

Sediment. — Usually considerable in quantity and consists 
chiefly of abnormal blood (possibly some normal blood if the 
irritation is at its height) ; few (or numerous) granular and 
brown granular, an occasional blood, epithelial, and fibrin- 
ous cast ; numerous renal epithelial cells, often colored 
brown, and a few leucocytes. 

Frequently there is evidence of a coexisting acute in- 
flammation of the pelvis of the kidneys, in which case 
small caudate cells from the superficial layer of the pelvis 
and clumps of cells from the calices will be found. 

Convalescence from a Severe Active Hyperemia. — In 
the severe forms of active hyperemia or catarrhal nephritis 
there is frequently a distinct convalescent stage, especially 
in those cases in which the source of irritation has been partly 
or entirely removed by natural means or by treatment. 

Character of the Urine. — Quantity. — The quantity is 
usually found to be above the average normal (1500 c.c), 
varying from 1600 to 2000 c.c. 

Color. — Slightly smoky or pale. 

Reaction. — Usually acid, unless mild diuretics, such as 
potassium acetate, may have been taken, when the reaction 
will be found alkaline from fixed alkalies. 

Specific Gravity.- — This varies as the twenty-four-hour 
quantity. It is generally between 10 12 and 10 18. 

Normal Solids. — Absolute. — The solids, especially the 
urea, are absolutely about normal. If for any reason the 
patient be kept on a low diet, of course the solids will be 
absolutely lower than when a liberal amount of nitrogenous 
food is given. Relatively^ the solids are diminished. 

Albumin. — This varies from the slightest possible trace 
to a large trace, usually the former. If the process be still 
rather active, the albumin may reach a large trace (about 
y^Q of I per cent). 

Sedimejit. — A few (sometimes numerous) abnormal blood 
globules. An occasional (or few) hyaline, finely granular, 
and brown granular casts, some with a little blood and fat, 
19 



290 DISTURBANCES AND DISEASES OF THE KIDNEYS. 

and a few with renal cells adherent. Few free renal cells, an 
occasional one slightly fatty. 

If there was a mild pyelitis during the acute stage of the 
disturbance, evidence of it may still be found — viz., little 
pus, free and in clumps ; small round cells, free and in the 
clumps of pus ; and, possibly, an occasional small caudate 
cell from the superficial layer of the pelvis of the kidney. 
In such a case leucocytes may be found on an occasional 
cast, especially those coming from the straight tubules. 

If the irritant has been entirely removed, the quantity of 
urine gradually falls to the normal, the casts disappear and 
finally the blood, at which time the urine will be found free 
from albumin — in other words, complete recovery. 

A circumscribed inflammation of one or both kidneys 
may take place, especially as a result of the extension of a 
gonorrheal or tubercular inflammation or other bacterial 
infection of the bladder and lower urinary passages to the 
renal pelvis, and then to circumscribed areas of the kidney. 
A circumscribed inflammatory process may also be set up 
around a crystalline deposit or morbid growth in the kid- 
ney. Under these circumstances the urine has the usual 
features of an active hyperemia, and not those of acute 
nephritis. 

There are very few clinical symptoms aside from the 
abnormal features of the urine, which are directly referable 
to this disturbance of the kidneys. In the majority of in- 
stances of mild active hyperemia renal symptoms are entirely 
wanting. Since an active hyperemia is always secondary, 
it may be stated in general that the symptoms encountered 
are those of the disease or abnormal condition that causes 
at, and not those that are referable to the kidneys them- 
selves. 

In the severer forms of this condition, particularly when 
due to mechanical irritants (crystals), pain in the loins is 
not uncommon. When due to exposure to cold and wet, 
pain in the loins, languor, headache, neuralgic pains in va- 
rious parts of the body, and more or less frequency of mic- 
turition are sometimes present. 

It is probable that an active hyperemia or active conges- 
tion of the kidneys always becomes a part of the initial 
stage of an acute nephritis. 

Dropsy never exists as a residt of an active hyperemia of 
the kidneys^ even when it is severe. 



PASSIVE HYPEREMIA. 291 

Differential Diagnosis. — From the urine alone it is 
often difficult, if not impossible, to distinguish between a 
severe active hyperemia (during its height) and an acute 
nephritis, owing to the fact that the albumin may be tem- 
porarily high, and the amount of blood and number of 
renal elements (casts and renal cells) abundant. By ob- 
serving the urine for a period of a few days, if a severe 
hyperemia, the amount of albumin and blood and the 
number of casts will be found to diminish rapidly. The 
urine will then have the characteristics of an ordinary 
active hyperemia, or the convalescent stage of this disturb- 
ance. In case the condition is one of acute nephritis the 
changes in the urine will be more gradual, and the three 
stages — i. e., acute, fatty, and convalescent, are easily dis- 
tinguished. The albumin will be abundant usually for a 
period of ten days or two weeks, and the amount of blood 
and the number of casts and renal cells will remain large. 

A urine secreted just before the fatal termination of a 
chronic interstitial nephritis may have all of the characteris- 
tics of a mild active hyperemia. The only features of such a 
urine pointing to a chronic nephritis are the low quantity 
of urine and the very low total solids. A consideration of 
the cHnical history and the symptoms is of the greatest 
importance in differentiating between these two conditions. 



PASSIVE HYPEREMIA. 

Passive hyperemia of the kidneys, also termed chronic 
passive congestion, is, like active hyperemia, not a disease 
of the kidneys, but a disturbance that is always secondary 
to some obstruction to the venous circulation. As a result 
of this, the kidneys are engorged with blood, and the 
urine becomes modified to a greater or less extent. 

Causes. — (i) Disease of the heart accompanied by ob- 
struction to the flow of blood through it. (2) Liver disease 
with obstruction to the passage of blood through the as- 
cending vena cava, whether due to marked enlargement or 
extensive atrophy (cirrhosis). (3) Tumors of the abdomen, 
including ih^ pregnant litems, may cause sufficient obstruc- 
tion to the circulation in the kidney to cause a passive hy- 
peremia. 

Character of the Urine. — Quantity. — In uncomplicated 
cases the twenty-four-hour quantity of urine is diminished, 



292 DISTURBANCES AND DISEASES OF THE KIDNEYS. 

usually varying from 400 to 1200 c.c, but is largely de- 
pendent upon the degree of obstruction and the character 
of the disease producing it. 

Color. — Generally high, especially if due to disease of the 
liver, or a markedly uncompensated heart. It may be 
normal or pale if due to a long-standing organic disease, or 
following treatment by diuretics. 

Reaction. — Usually strongly acid ; when the urine is 
dilute and of low specific gravity, the reaction is either nor- 
mal or faintly acid. 

Specific Gravity. — This varies inversely as the quantity, 
and directly as the metabolism. If the urine is high col- 
ored and concentrated, it will have a specific gravity varying 
between 1025 and 1035. On the other hand, if the urine 
is pale and less concentrated, it will vary between 1012 
and 1020. 

Normal Solids. — Absolute. — Usually considerably di- 
minished, especially if the cause of the disturbance is 
marked. Since there is more or less dropsy accompanying 
the heart or liver disease, the chlorides and urea will be 
found absolutely diminished. (See Effect of Dropsy upon 
the Solids.) Relative. — Increased, especially the uric acid. 
In extreme cases accompanied by marked dropsy the urea 
and chlorides will be relatively diminished. 

Albumin. — This varies between the sligJitest possible trace 
and -^ of I per cent, (except in pregnancy, when it may 
exceed this quantity). The amount of albumin is generally 
a very slight trace or a trace. 

Sediment. — Frequently there is a deposit of amorphous 
urates. An occasional (or few) hyaline and finely granular 
cast of small diameter. Rarely, a renal cell, and very 
rarely, a blood globule (blood is often absent). If more 
than a stray blood globule be present, it is usually either 
accidental or the result of some slight complication. Fat 
globules are not found in the cells or adherent to the casts, 
except in case there is some active parenchymatous change 
as a complication. 

Not infrequently a passive hyperemia is complicated by 
an active hyperemia, in which case a few blood globules 
(abnormal) will be found free and adherent to casts. (See 
Differential Diagnosis.) 

Passive Hyperemia of Pregnancy. — The urine of a preg- 
nant woman, especially between the seventh and ninth 



PASSIVE HYPEREMIA. 293 

months, will almost invariably show more or less evidence 
of a passive hyperemia of the kidneys. Most of these 
cases pass a urine having the characteristics of passiv^e 
hyperemia already described, except that in pregnancy it is 
not common to find a highly concentrated or highly colored 
urine, but rather one having a normal or pale color, and a 
normal or slightly low specific gravity. 

Occasionally, the renal disturbance is severe, when the 
albumin usually exceeds -jlg- of i per cent., and may go as 
high as i of i per cent. 

The renal casts in the sediment are frequently of larger 
diameter than those found in the sediment of an ordinary 
passive hyperemia due to heart or liver disease. 

The symptoms encountered in passive hyperemia are 
those of the disease or disturbance that causes the passive 
congestion of the kidneys ; there are usually no symptoms 
that are directly referable to the kidneys themselves. There 
is generally dropsy, mostly of the feet and legs ; dyspnea ; 
edema of the lungs, which causes a hacking cough ; and 
prominence of the veins of the abdomen. 

Differential Diagnosis. — The diagnosis of an uncom- 
plicated passive hyperemia of the kidneys can usually be 
made from the urine without a knowledge of the clinical 
history or physical examination. If, however, the condi- 
tion is complicated in any way, either by an active hyper- 
emia, acute nephritis, or by some chronic disease of the 
kidneys, the diagnosis of passive hyperemia can not be 
made with certainty from the urine alone. 

In the passive hyperemia of pregnancy a rapid increase in 
the quantity of albumin and an increase in the number of 
hyaline and finely granular casts in the sediment are always 
important, as these changes frequently serve as a " danger 
signal " to the approach of puerperal eclampsia. It must be 
borne in mind, however, that puerperal convulsions may 
occur without there being necessarily any marked change 
in the quantity of albumin or the appearance of blood. 
Nevertheless, this fact does not lessen the importance of 
carefully watching the urine for such changes as may indi- 
cate the approach of this serious complication. It is a well- 
known fact that chronic diseases of the kidney do not pre- 
dispose to the occurrence of puerperal eclampsia, even 
though a passive hyperemia is superimposed. 

Passive congestion of the kidneys is to be distinguished 



294 DISTURBANCES AND DISEASES OF THE KIDNEYS. 

from a chronic interstitial nephritis chiefly by the large quan- 
tity of urine and the low absolute quantity of urea in the 
latter disease. Also by the predominance in interstitial dis- 
ease of the quantity of urine passed at night over that passed 
during the day, and by the prominent symptoms of intersti- 
tial nephritis — i. ^., a full, hard pulse, cardiac hypertrophy, 
absence of dropsy until late in the disease, etc. — all of which, 
except dropsy, are absent in passive hyperemia. In chronic 
interstitial nephritis near death, when the quantity of urine 
has fallen to the normal or below, it is frequently impossible 
to distinguish between these two conditions. 

ACUTE DIFFUSE NEPHRITIS (ACUTE NEPHRITIS), 

This condition consists of an acute inflammation or 
degeneration of the kidneys ; the pathologic process is 
usually present in both kidneys, although it may be entirely 
confined to one of these organs. According to Councilman, ^ 
an acute diffuse nephritis includes a number of pathologic 
conditions : i. c. — 

''(a) Acute Degenerative Nephritis. — In this are in- 
cluded degenerative lesions of the epithelium, embracing 
cloudy swelling, hyaline, fatty, and dropsical degeneration, 
and often complete necrosis, without lesions other than 
degenerative, in the glomeruli or in the interstitial tissue. 
This occurs chiefly in infectious diseases, in jaundice, in 
anemia, and as the result of the action of certain poisons. 
The kidney is slightly swollen or unchanged in size, rather 
paler and more opaque on section ; the markings may be 
obscure or more prominent than normal. There is often 
albuminous exudation in the glomerular capsules and in the 
tubules. 

(b) Acute Glomerular Nephritis. — The essential 
changes consist in acute lesions in the glomeruli. There 
may be acute proliferation of the endothelium of the vascular 
tufts, hyaline and fibrinous thrombi in the vessels, accumula- 
tion of leucocytes in the vessels, degeneration of the vessel 
wall, etc. These changes in the vascular tufts of the glomer- 
ulus can occur with or without changes in the capsular epi- 
thelium. The changes in the capsular epithelium consist in 
degeneration and proliferation. The capsular space may 
contain an albuminous hemorrhagic or fibrinous exudation. 

1" Amer. Journ. Med. Sciences," July, 1897. 



ACUTE DIFFUSE NEPHRITIS. 295 

The changes in the vascular tufts and in the capsule are so 
frequently combined in various degrees that they can not be 
separated into two subclasses. The glomerular lesions are 
accompanied by degeneration of the tubular epitheHum, 
necrosis, and exfoliation. Often there are dilatation of the 
tubules and edema and cellular proliferation of the inter- 
tubular tissue. There may be more or less hemorrhage into 
the tubules. 

This affection occurs in infectious diseases, notably in acute 
endocarditis, measles, and diphtheria, or as an independent 
affection. The kidney is usually increased in size. The 
capsule easily strips off; the surface is pinkish and mottled 
with points of ecchymosis. On section the cortex is wide, 
rather paler and more opaque, markings obscure ; glomeruli 
pale, enlarged, and prominent. Pyramids often congested. 
The tissue moist and pits on pressure. While these appear- 
ances are usually marked, lesions of the glomeruli may be 
found with but Httle macroscopic change in the kidney. 

(c) Acute Hemorrhagic Nephritis. — The essential 
change consists in hemorrhage in the tissue combined with 
degeneration of the epithelium. The hemorrhage is chiefly 
found in the capsule of the glomeruH and in the tubules. 
The degenerative lesions may be extensive and lead to 
necrosis and exfoliation. Edema, hemorrhage, and cellular 
infiltration are often found in the intertubular tissue. The 
kidney is enlarged, hemorrhages are found in the capsule ; 
the surface is dark red, with numerous ecchymoses. On 
section the cortex is swollen and sprinkled with dots and 
streaks of ecchymosis. 

(d) Acute Interstitial Nonsuppurative Nephritis. — 
The essential lesion consists in acute proliferation of the cells 
in the intertubular tissue. The proliferation takes place 
mainly from the vascular endothelium. The cells lie within 
and without the vessels. They are large and similar to the 
endothelial cells of young granulation tissue. They are 
found chiefly in the intermediate zone of the kidney between 
the pyramids and the cortex. In the cortex they are both 
generally diffused and in areas chiefly around the glomeruli. 
There is more or less degeneration and necrosis of the 
tubules, affecting chiefly those in the areas of cellular infil- 
tration. Leucocytes in small numbers may be found in the 
intertubular tissue among; the other cells, in the degenerated 
epithelium, and in the lumen of the tubules. The glomeruli 



296 DISTURBANCES AND DISEASES OF THE KIDNEYS. 

are not affected. This affection occurs in acute infectious 
diseases, notably in diphtheria and scarlet fever. The kidney 
is large, pale, somewhat mottled ; on section, moist, opaque, 
markings obscure, and milky fluid can be pressed from it." 

From a clinical point of view we are unable at present to 
distinguish with certainty between these four forms of acute 
nephritis, either by the characteristics of the urine or by a 
consideration of the urine in connection with the clinical his- 
toiy and symptoms. The description that follows applies 
to an acute nephritis as seen clinically, and is without refer- 
ence to these different forms of the disease. It is probable, 
however, that the form which Councilman designates as 
** acute degenerative nephritis " corresponds to the condition 
which the author has described as active hyperemia. 

Causes. — An acute nephritis may be caused by any irri- 
tant or abnormal condition, such as causes an active hyper- 
emia (see Causes of Active Hyperemia) ; in fact, an active 
hyperemia from any cause may end in a true acute nephritis. 
Of the causes exposure to cold and zvet is probably the most 
common. Toxines, notably those of diphtheria and scarlet 
fever, are very apt to cause acute nephritis. Bacterial in- 
fection is sometimes a cause, and when present, generally 
produces the disease in its most virulent form. In preg- 
nancy there may be an acute nephritis, w^hich is usually ac- 
companied by puerperal convulsions, and not infrequently 
this complication proves fatal. 

An acute nephritis may be divided into three stages : First 
or acute, second or fatty, and tJiird or convalescent stage. 

First or Acute Stage. — 

Character of the Urine. — Quantity. — Much diminished 
— usually 200 to 400 c.c. There may be almost complete 
anuria, the patient frequently passing not more than 100 c.c. 
in forty-eight hours. 

Color. — Very smoky (dark) or, in the first day or two, 
almost black ; if much normal blood, a blood-red color. 

Reaction. — Usually acid ; sufficient blood may be pres- 
ent to give a slightly alkaline reaction. 

Specific Gravity. — Generally high, although it may be 
low. If albumin be present in large amount (and it gener- 
ally is excessive), it will raise the specific gravity to 1030, 
even though the normal solids are diminished. 

Normal Solids. — Absolutely, much diminished, espe- 



ACUTE DIFFUSE NEPHRITIS. 297 

dally the urea and chlorine. (See Effect of Dropsy on 
Normal Solids.) If the dropsy is increasing, as is the rule 
during this stage, the chlorine may be found absent. Rela- 
tively, diminished, especially the urea and chlorine. 

Albumin. — Generally ^i^ to ^ of i per cent. It may 
exceed this quantity, going as high as i J^ per cent. The 
amount varies with the severity of the disease and the degree 
of obstruction in the tubules. 

Sediment. — Abundant and of a dark -brown or choco- 
late color. It consists of a large number of abnormal, and 
perhaps some normal, blood globules. Many brown 
granular renal epithelial cells. Many brown granular, 
epithelial, blood, and fibrinous casts, and perhaps a few 
hyaline and finely granular casts. A large amount of 
granular debris from the broken-down renal cells and blood 
globules. There are usually numerous leucocytes, free, in 
clumps, and adherent to the casts ; also small caudate cells 
from the superficial layer of the pelvis, as well as an occa- 
sional clump of round cells from the calices of the kidney 
— an acute pyelitis. 

The duration of this stage is usually from five to ten 
days. The urine then commences to show signs of im- 
provement, the dropsy begins to diminish, the absolute 
solids are a little higher, the quantity of urine gradually in- 
creases, and fatty elements begin to appear or have already 
appeared. 

Second or Fatty Stage. — 

Character of the Urine. — Quantity. — This varies be- 
tween 800 and 1500 c.c, according to the amount of im- 
provement that has taken place. 

Color. — Still very smoky. 

Reaction. — Usually acid. 

Specific Gravity. — This generally ranges between 10 15 
and 1020. It is still influenced by the considerable amount 
of albumin that is present. 

. Normal Solids. — Absolutely, somewhat diminished, al- 
though higher than in the first stage. Relatively, dimin- 
ished. The urea and chlorine will be found relatively 
higher as the dropsy diminishes. 

Albumin. — This varies between yi and ^ of i per cent. 
As a rule, the diminution in the quantity of albumin is in 
inverse proportion to the increase in the twenty-four-hour 



298 DISTURBANCES AND DISEASES OF THE KIDNEYS. 

quantity of urine. In the first part of this stage the quan- 
tity of albumin may exceed ^ of I per cent. 

Sediment. — This is still abundant in quantity, and of a 
brown color. The elements are practically the same as in 
the acute stage, but with the addition of fatty renal cells, 
fatty casts, and compound granule cells. The amount of 
fat at this time follows quite closely the degree of severity 
of the disease during the acute stage — that is, if there was a 
rather mild acute stage, the number of fatty elements and 
the degree of degeneration will not be extensive ; but if 
there was a severe acute stage, the quantity of fat will be 
excessive. Furthermore, from a single examination of the 
urine at this time, and without a knowledge of the previous 
history, it may be impossible to determine whether we are 
dealing with the fatty stage of an acute nephritis or a sub- 
acute glomerular nephritis that is complicated by an acute 
process. 

The evidences of a pyelitis seen in the acute stage will 
probably be present to a greater or less extent in this stage, 
although it occasionally happens that the acute pyelitis 
has developed into a subacute or chronic pyelitis. The 
latter is shown by the presence of a larger quantity of pus, 
free, arranged in clumps, and adherent to casts of large 
diameter ; also a large number of small round cells, free 
and in the clumps of pus. 

The duration of this stage is about the same as that of 
the first, — viz., five to ten days, — providing there is steady 
improvement. 

With the favorable progress of the disease the character 
of the urine gradually changes still more, and we have the 
third or convalescent stage. The edema has entirely dis- 
appeared. 

Third or Convalescent Stage. — 

Character of the Urine. — Quantity. — This generally 
varies between i 500 and 3000 c.c. There is usually a gradual 
rise in the quantity, as high as 4000 c.c, where it gener- 
ally remains for a few days or even weeks. As the condi- 
tion approaches complete recovery, the quantity falls 
gradually, and in some cases there is a sudden fall to about 
the normal. 

Color. — Usually, the urine has lost its smoky color and 
is pale. Occasionally, the smoky color continues, especi- 



ACUTE DIFFUSE NEPHRITIS. 299 

ally in the early part of this stage, and as long as the urine 
contains a large amount of abnormal blood. As the amount 
of blood diminishes, the color becomes pale. 

Reaction — Faintly acid. 

Specific Gravity. — This varies as the quantity — /. e., if 
the twenty-four-hour amount is between 3000 and 4000 c.c, 
it will be not far from 1008 to 10 10. On the other hand, 
if the quantity is between 1800 and 2500 c.c, it will be be- 
tween 10 1 2 and 10 1 8. 

Normal Solids — These are absohitdy normal. They may 
be increased for a time, especially the urea and chlorides, 
due to their reabsorption from the serous transudations and 
their elimination in the urine. They are relatively dimin- 
ished, the degree of diminution being dependent upon the 
dilution of the urine. 

Albumin — This is usually between yi of i per cent, and 
a very slight trace, according to the extent of the convales- 
cence and the twenty-four-hour quantity of urine. The 
larger the quantity of urine, the smaller the amount of al- 
bumin. The average quantity in this stage will be not far 
from a trace. 

Sediment — Generally, slight in quantity and colorless, 
although it may still have a brownish color if much abnor- 
mal blood be present. It consists of numerous (or few) 
abnormal blood globules. Few (or occasional) hyaline, 
granular, and brown granular casts, and rarely a blood, 
epithelial, and fibrinous cast. Most of the casts with 
abnormal blood and a little fat adherent. Few renal cells, 
some fatty. Rarely there may be a small fatty cast. The 
brown granular and fibrinous casts are the first to disappear. 

If there was a chronic pyelitis in the second stage, evi- 
dence of it will probably still be found. As the convales- 
cence advances, the pyelitis usually disappears rather sud- 
denly, if it has not entirely recovered during the second 
stage. 

The duration of the convalescent stage is from one to 
four months, but not infrequently it lasts for a longer period, 
even from one to two years, followed by complete recovery. 

In a perfectly favorable convalescent stage, without com- 
plications, after the lapse of a month or two, the quantity 
of urine falls to the normal, the albumin diminishes to a very 
slight trace or the slightest possible trace, the quantity of blood 
diminishes, the brown granular and fibrinous casts disap- 



300 DISTURBANCES AND DISEASES OF THE KIDNEYS. 

pear and then the majority of the fatty elements. In well- 
advanced convalescence, only hyaline and granular casts, an 
occasional blood globule free and adherent to some of the 
casts, an occasional renal cell, and rarely a fatty renal cell 
remain. If the urine is first examined at this time and with- 
out a knowledge of a previous history of the case, it is often 
impossible to determine whether the condition is one of 
active hyperemia or a well-advanced convalescence from an 
acute nephritis, for the urine is the type of one of simple 
active hyperemia. When complete recovery has taken 
place, all abnormal elements disappear from the sediment, 
and the urine is normal in character. 

The prognosis in a case of acute nephritis is usually 
good, although there is always a liability that it may result 
in a chronic disease of the kidneys. It is certainly the ex- 
ception, and not the rule, for an acute nephritis to run as 
favorable a course as has just been outlined. 

Exacerbations (relapses) are very liable to occur, espe- 
cially during the convalescent stage. 

Causes. — Probably the most common cause is exposure 
— a draft of air on the head and neck, too little clothing, 
cold and wet feet, etc. Since the skin is usually very active 
at this time, any sudden exposure stops its action and in- 
creases the congestion or inflammation of the kidneys. Oc- 
casionally, the ingestion of highly nitrogenous food (meats, 
etc.) is apparently an element in causing an exacerbation. 
Sometimes an exacerbation occurs without a discernible 
cause, even when the patient has taken every precaution. 
The onset is usually sudden, and the patient realizes that 
he does not feel as well as usual, having a recurrence of the 
symptoms of the acute stage — i. e., diminished quantity of 
urine, frequent micturition, and generally some headache and 
pain in the back. There is usually more pallor than before 
the attack, and often swelling of the face and extremities. 

Character of the Urine. — The urine of an exacerbation 
is characterized (i) by a sudden fall in the quantity, (2) a 
blood-red color, and (3) the presence in the sediment of a 
large quantity of normal blood. It may be either mild or 
severe, and the severity of the attack governs the extent to 
which the quantity of urine is diminished, and the amount of 
normal blood found ; in other words, if severe, the quantity 
of urine is greatly reduced and the amount of normal blood 
large ; if mild, a moderately diminished quantity and com- 



ACUTE DIFFUSE NEPHRITIS. 301 

paratively little blood. The quantity of albumin increases 
and the normal solids diminish according to the severity. 
The blood, epithelial, and fibrinous casts are again present in 
moderately large numbers. In the course of two or three 
days, possibly a week or ten days, the urine again increases 
and the normal blood disappears, although the latter may 
continue in small amount (not sufficient to give the urine a 
bloody color) for weeks. Following the disappearance of 
the greater part of the normal blood, the urine generally 
contains a larger quantity of abnormal blood than before 
the exacerbation, hence a smoky color again for a few days. 
After a short time has elapsed the urine again presents the 
characteristics of the third, or convalescent, stage of an acute 
nephritis. 

Any number of exacerbations may occur, the average 
being from one to four, and the larger the number, the more 
prolonged the convalescence. Likewise, the greater the 
number of exacerbations, the more extensive the pathologic 
changes in the kidney, and hence the more unfavorable 
the prognosis, since the acute nephritis may end in a chronic 
disease of the kidneys. An unfavorable prognosis is not 
necessarily warranted, however, as cases of acute nephritis 
accompanied by frequent exacerbations have recovered after 
a lapse of two years. 

Symptoms of tiremia may appear at the time of a severe 
exacerbation because of the interference with the elimination 
of the toxic material from the body ; but, fortunately, this 
complication is only rarely seen. 

Prominent Symptoms. — The onset of an acute nephritis 
is usually very rapid and, like other acute processes, is fre- 
quently ushered in by a chill. There is usually rapid pallor, 
swelling of the lower eyelids and face, also edema of the legs, 
and often general dropsy ; intense headache, thirst, nausea, 
and often vomiting ; pain in the back and limbs, and 
frequency of micturition. Because of the last-mentioned 
symptom the patient often has the firm impression that he is 
passing a large quantity of urine, but when the total 
quantity is measured, it will be found to be abnormally 
diminished. There is usually at first some elevation of tem- 
perature, also a high tension pulse. Acute uremic symp- 
toms are not uncommon, the most prominent of which are 
nausea and vomiting, stupor, and sometimes convulsions. 
Acute visual disturbances are occasionally seen. 



302 DISTURBANCES AND DISEASES OF THE KIDNEYS. 

Differential Diagnosis. — The distinction between a 
severe active hyperemia and a mild acute nephritis is, in some 
instances, not easily deduced from the urine alone. How- 
ever, the history of a sudden onset and the prominent symp- 
tom of edema, — swelling of the face and legs,— together with 
the chief characteristics of the urine — viz., the persistence 
of a considerable amount of albumin, considerable blood, 
and numerous casts — will serve to distinguish an acute 
nephritis from a severe form of active hyperemia. 

The urine of the second stage of aciUe nephritis may not 
differ materially from one of subacute glomerular nephritis 
(active stage) complicated by an acute process. In the latter 
condition the albumin is usually present in larger amounts, 
and the total quantity of urea is generally much lower than 
in the former disease. In an acute nephritis the clinical 
symptoms will show that the condition is gradually improv- 
ing, while in a case of a complicated subacute glomerular 
nephritis the patient is at his worst. In doubtful cases, 
however, the urine should be carefully watched for several 
days ; if an acute nephritis, the third or convalescent stage 
will appear ; if a subacute glomerular nephritis complicated 
by an acute process, the acute complication will gradually 
subside, leaving the disease in its uncomplicated form ; or 
the patient may have symptoms of uremia and succumb to 
the disease. 

The urine of the convalescent stage of an acute nephritis 
should not be mistaken for the urine of chronic interstitial 
or chronic diffuse nephritis. The acute history, the charac- 
teristic first and second stages of an acute nephritis, the 
presence of blood in the sediment, and the normal total solids 
will serve to distinguish an acute from a chronic form of renal 
disease. 

SUBACUTE GLOMERULAR NEPHRITIS. 

Subacute glomerular nephritis, also termed " chronic par- 
enchymatous nephritis," *' fatty degeneration of the kid- 
neys," and " chronic diffuse nephritis of the parenchymatous 
type," is a disease characterized by marked degenerations 
of the glomeruH as well as of the epithelial lining of the 
renal tubules. 

The essential lesions are in the glomeruli. They consist 
in swelling and nuclear increase in the vascular tufts and 
obliteration of the vessels by hyaline degeneration, both of 



SUBACUTE GLOMERULAR NEPHRITIS. 303 

the cells and the vascular walls. These changes in the tufts 
are often combined with proliferation and desquamation of 
the capsular epithelium with connective-tissue ingrowth. 
There is extensive degeneration, necrosis, and desquamation 
of the tubular epithelium. The intertubular tissue is the 
seat of edema and connective-tissue formation. The kidney 
is enlarged, and the capsules may cling slightly to the sur- 
face, which is pale and slightly mottled. On section, the 
cortex is increased in width, pale, opaque, markings obscure, 
glomeruli pale, and its consistency is increased (Council- 
man). 

Causes. — This disease is sometimes the result of a pre- 
vious acute nephritis, during the course of which frequent 
exacerbations have occurred, and when the convalescence 
has been extended over a long period (years). It is, per- 
haps, more common for the disease to accompany chronic 
wasting diseases, such as phthisis, syphilis, and chronic 
suppurative bone diseases ; also in cases of prolonged 
malaria. When the disease is an accompaniment of these 
conditions, the changes in the kidney are gradual, and the 
disease appears to be chronic from the beginning. The rea- 
son for a subacute glomerular nephritis under these circum- 
stances is not known. 

The disease can be conveniently divided into two stages — 
i. e.y active and inactive stages. 

ACTIVE STAGE. 

This stage is seen at the time when the patient is at his 
worst. The urine is concentrated and highly characteristic, 
and there is marked dropsy. 

Character of the Urine. — Quantity. — Very small, vary- 
ing from 200 to 800 c.c, the average being not far from 
400 c.c. 

Color. — High, like that of a fever urine, and often turbid 
because of the presence of amorphous urates. In case of 
a recent acute exacerbation, the color will be bloody. 

Reaction. — Usually strong acid. 

Specific Gravity. — High — 1026 or 1028, and often as 
high as 1030 or 1035. 

Normal Solids. — Absolutely, much diminished, especially 
the urea and chlorides, which are low because of the very 
extensive and increasing dropsy. The chlorides may be 



304 DISTURBANCES AND DISEASES OF THE KIDNEYS. 

nearly absent. Relatively, the uric acid and the urea are in- 
creased, unless the disease has been going on for a long 
time, in which case the urea will be relatively diminished. 
The chlorides are much diminished or nearly absent. 

Albumin. — In this form of kidney disease, and especially 
in this stage, the quantity of albumin is the largest ever found 
in the urine. It varies between ^ of i and 3 or 4 per cent, 
by weight, but the average quantity is usually from i^ of i to 
I per cent. The maximum amount ever reported was as high 
as 5 per cent. Upon performing the heat test for albumin 
it is not very uncommon to find that the urine completely 
solidifies, in which case the quantity of albumin exceeds 2 
per cent. The average quantity in this stage is between ^ 
of I and I per cent., usually nearer the latter figure. 

Sediment. — If a deposit of amorphous urates is present, 
the sediment will be abundant and usually of a pink or red- 
dish-brown color. If there is not a deposit of urates, the 
amount of sediment will be '' considerable " and practically 
colorless. If the disease be complicated by an acute pro- 
cess, normal blood may be present in sufficient quantity to 
color the urine and sediment red. The sediment consists of 
many hyaline, granular, and fatty casts, some of which have 
fatty renal and compound granule cells adherent ; numer- 
ous /r^^ fatty renal and compound granule cells. Crystals 
of the fatty acids are often seen projecting from the fatty 
renal and compound granule cells, and the fatty casts. 
Cholesterin crystals are occasionally seen, but usually only 
in the late stages of the disease. If the disease is well ad- 
vanced, waxy casts may be seen in the sediment. When 
present, they are of bad omen. In an uncomplicated case the 
sediment is free from blood and renal blood elements. As a 
matter of fact, chronic diseases of the kidneys are usually 
more or less complicated by either a mild or severe acute pro- 
cess, so that usually an occasional (or numerous) blood 
globule will be found. If there is very much blood present, 
a few leucocytes are often found free and adherent to some 
of the casts. 

With the improvement that usually follows rest in bed, 
a milk diet, and mild diuretic treatment, providing the dis- 
ease is not near its termination, there is a distinct change in 
the character of the urine. The dropsical effusions have 
diminished, the edema of the extremities has largely disap- 
peared, although usually not entirely, and the process in the 



SUBACUTE GLOMERULAR NEPHRITIS. 305 

kidneys appears to be quiescent. Then we have the inac- 
tive stage of the disease. 

INACTIVE STAGE, 

Character of the Urine. — Quantity. — Usually, from 
800 to 1200 c.c. It may exceed the normal quantity for a 
day or two at the time the edema is being absorbed, but 
it soon falls to about 1200 c.c. 

Color. — The color is pale and not infrequently the urine 
has a greenish tint. 

Reaction. — Generally, acid. 

Specific Gravity. — This varies as the twenty-four-hour 
quantity, but in the early part of the disease it will gen- 
erally vary between 10 10 and 10 15. 

Normal Solids. — They are both absohttely and relative- 
ly diminished. The solids may be absolutely somewhat 
higher than in the active stage, especially at the time of the 
greatest absorption of the edema, but the increase is usually 
slight. 

Albumin. — The quantity of albumin is smaller than in 
the active stage, but it is still present in large amount, gen- 
erally from i^ to i^ of I per cent. Occasionally, it is a 
little less than j^ of i per cent., particularly if the twenty- 
four-hour quantity of urine is about 1500 c.c. 

Sediment. — This is " considerable " in quantity, and 
colorless. A deposit of amorphous urates is usually not 
present. It consists of the same elements that were found 
in the active stage, but they are less in number : numerous 
hyaline, granular, and fatty casts, fatty renal and compound 
granule cells. If waxy casts were present in the active 
stage, they will be found at this time, although fewer in 
number. Crystals of the fatty acids and cholesterin will 
also be found if they were present in the active stage. 

ATROPHIC STAGE. 

This stage is only very rarely seen, since death usually 
occurs before atrophy of the kidneys has taken place. The 
kidneys become very small, have a yellow color, consist 
principally of fat, and there is a marked increase in the con- 
nective tissue. 

Character of the Urine. — The quantity oftirine is usually 
not far from the normal, and it may be slightly increased. 



306 DISTURBANCES AND DISEASES OF THE KIDNEYS. 

The specific gravity and the normal solids are very low ; the 
quantity of albumi7i falls to about ^ of i per cent, or less ; 
and the sedimejit consists of practically the same elements 
as in the inactive stage of the disease, except a smaller 
number of fatty elements and a larger proportion of waxy 
casts. 

A subacute glomerular nephritis is characterized by fre- 
quent alternations of the active and passive stages, without 
there being necessarily a true acute exacerbation. But 
acute exacerbations are as likely to occur in this disease 
as in an acute diffuse nephritis. When present, the urine 
has the additional elements of the acute disease, together 
with the normal blood and renal blood elements — blood- 
casts, etc. 

Prominent Symptoms. — The patient usually suffers from 
indigestion (early symptom), often attended with vomiting ; 
almost constant headache, which gradually increases in in- 
tensity from month to month ; marked pallor ('* pasty") and, 
usually, swelling of the face ; and invariably marked edema 
of the extremities, which finally extends and increases to a 
condition of extreme general dropsy (ascites, pleuritic effu- 
sion, etc.). There is frequency of micturition, but a small 
quantity of urine is passed. Palpitation and dyspnea on ex- 
ertion are often present to a marked degree. The disease 
is characterized by periods of activity in which the edema 
is increased, the quantity of urine is very small, and 
there are uremic symptoms. It is also characterized by 
quiescent periods, in which the patient improves, the edema 
diminishes, and the quantity of urine increases, although 
generally not above the normal except for a day or two. 

The duration of the disease is usually from two to five 
years, but this depends upon the care of the patient and 
the hygienic surroundings. If the circumstances are such 
that he can have the very best care, life may be pro- 
longed a year or two longer ; on the other hand, an 
early end is often the fate of such cases among the poorer 
classes. 

The prognosis is invariably unfavorable. So far as is 
known, recovery never takes place after the disease has be- 
come well established. Death may result from uremia or, 
as is not infrequent, from some secondary acute disease, 
such as pneumonia, erysipelas, diphtheria, etc. The low 
physical state of the patient renders him very susceptible 



CHRONIC INTERSTITIAL NEPHRITIS. 307 

to other diseases, especially those of an acute infectious 
nature. 

Differential Diagnosis. — The diagnosis of a subacute 
glomerular nephritis from the urine alone is generally not 
difficult, providing the condition is uncomplicated. In case 
the disease is complicated by an acute process it can not be 
readily distinguished from the second stage of an acute 
ncpJiritis. Under these circumstances the history of the 
case should be considered, and the character of the urine 
should be carefully watched for several days. If a compli- 
cated subacute nephritis, the acute process will generally 
subside in the course of from two to three weeks, when the 
urine will have the characteristics of an uncomplicated sub- 
acute nephritis. The edema that was extreme at first 
usually continues after the acute process has subsided — viz., 
after the blood has entirely disappeared. On the other 
hand, if the disease is an acute nephritis passing through the 
second stage, the third or convalescent stage will soon ap- 
pear, the edema will entirely subside, and the patient will 
gradually improve until there is complete convalescence. 

CHRONIC INTERSTITIAL NEPHRITIS. 

This condition has been variously termed chronic neph- 
ritis, chronic diffuse nephritis of the interstitial type, sclerotic 
kidney, gouty kidney, small gramdar kidney, chronic diffuse 
nephritis zvithout exudation, etc. It is a chronic disease of 
the kidneys, which is characterized chiefly by an increase in 
the connective tissue of those organs. The disease develops 
very slowly and insidiously, usually having been in prog- 
ress for years before it is recognized, and then often only 
accidentally discovered by the physician who is consulted 
for the relief of headaches or some annoying stomach diffi- 
culty ; or perhaps it is first encountered by the life insur- 
ance examiner or oculist. 

According to Councilman, some of the pathologic pro- 
cesses found in chronic interstitial nephritis, such as cJironic 
arteriosclerotic nephritis, and chronic degenerative and inter- 
stitiat nephritis really belong under the heading of chronic 
diffuse nephritis. 

In chronic arteriosclerotic 7tephritis the essential lesions 
occur in the arteries, and consist in those changes known 
as arterioscleroses. There is degeneration of the epi- 



308 DISTURBANCES AND DISEASES OF THE KIDNEYS. 

thelium of the tubules, with more or less complete de- 
struction. The degeneration takes place slowly, and at 
any given time sections may show only a slight degree. 
Atrophic changes in the epithelium are common. The 
lesions may affect almost equally all parts of the kidney, or 
appear in areas corresponding to the vascular territories of 
those arteries that are most affected. There is a general 
increase in the connective tissue, though large areas of 
tubules may be found with no increased tissue between 
them. This condition of the kidney is found accompany- 
ing a general arteriosclerosis affecting all the arteries of the 
body, or the vascular lesions may be most marked in the 
renal arteries. The kidney varies in size ; it may be 
slightly larger or of normal size, but is usually very much 
smaller than normal. The capsule may or may not be 
adherent. The surface is more or less irregular and granu- 
lar ; the color is red and often cyanotic. On section, the 
cortex may be much diminished in size, of a dark-red 
color, the markings obscure, and the glomeruli injected ; 
the arteries in the intermediate portion are evident, and often 
project above the cut surface. The pyramids show venous 
congestion ; the consistency of the kidney is greatly in- 
creased. Most of the cases of contracted kidney belong to 
this class. 

To the class of chronic degenerative mid interstitial neph- 
ritis belong those cases of contracted granular kidney that 
occur without primary arterial lesions. It is difficult to give 
a name to the condition, for there is no single change 
that predominates. Degeneration, atrophy, and destruc- 
tion of the epithelium in various degrees are found. There 
is a general increase in connective tissue more diffuse than 
in the arteriosclerotic nephritis, but not so diffuse as in the 
chronic glomerular form. The increase in the connective 
tissue is most intense where the degeneration of the epithe- 
lium is most marked. Lines of connective tissue extend to 
the surface, and by their contraction produce depressions. 
Very minor degrees of change, which may consist in small 
areas of cellular infiltration with hyperplasia of the connec- 
tive tissue extending down from the capsule, are very com- 
monly found. The essential lesion seems to be a slow 
degeneration of the epithelium, followed by connective-tis- 
sue hyperplasia. The microscopic appearances of the kid- 
ney vary extremely, following the different degrees of the 



CHRONIC INTERSTITIAL NEPHRITIS. 309 

lesions. The gross and microscopic condition may be com- 
plicated by lesions of another character (Councilman). 

Causes. — There are three toxic agents that are probably 
causes of this disease : 

1. Lead. — Chronic lead-poisoning is usually met with in 
type-setters, painters, those handling lead, and others ex- 
posed to its influence. The damage to the kidneys is 
apparently due to the constant elimination of the lead, which 
acts as a chemic irritant. The connective -tissue changes 
do not usually appear until after years of almost constant 
poisoning. 

2. Alcohol. — -Those persons who are addicted to the 
moderate use of alcohol, especially if continued for years, 
may have a chronic interstitial nephritis, which may lead to 
their death or be an accompaniment of some other acute or 
chronic disease that proves fatal. 

3. Uric Acid. — The gouty individual is often the victim 
of this disease— the so-called " gouty kidney." The man- 
ner in which uric acid produces a chronic interstitial nephri- 
tis can not be well explained unless we assume that it is the 
result of the constant irritation set up by the elimination of 
excessive amounts of uric acid and other products of 
diminished metabolism. 

Arsenic. — Chronic arsenic-poisoning probably leads to 
this form of disease, especially in those persons who have 
been exposed to the influence of the substance for a long 
period of years. 

Syphilis and chronic malaria are also considered 
causes of this disease. It is certain that these conditions 
are often accompanied by a chronic interstitial nephritis, but 
not invariably. It is probable that any long-continued irri- 
tation of the kidneys gradually results in renal changes 
that finally terminate in a chronic interstitial nephritis. 

Arteriosclerosis. — There can be no doubt that this dis- 
ease of the blood-vessels results in those changes that 
characterize this form of kidney disease. It is common in 
middle-life, and, as before stated, most of the cases of con- 
tracted kidney belong to this class. 

Chronic interstitial nephritis can be divided, clinically, 
into three stages according to the degree to which the urine 
becomes modified from the normal and the extent of the 
renal changes : first or early stage, second or advanced 
stage, and third or late stage. 



310 DISTURBANCES AND DISEASES OF THE KIDNEYS. 



FIRST OR EARLY STAGE. 

This stage is seen at the time when the individual is 
capable of attending to business and, with the exception of 
headaches and frequent attacks of indigestion, enjoys a fair 
degree of health. There may not be any noticeable fre- 
quency of micturition at this time, although the patient will 
probably find it necessary to urinate once or twice during 
the night. 

Character of the Urine. — Quantity. — This is a very 
important element in the diagnosis. It is moderately in- 
creased above the normal at this time — usually, between 
1500 and 2000 c.c. Frequently, the quantity of urine 
passed at night exceeds that passed during the day ; this 
is much more marked during the advanced stage of the 
disease. 

Color. — Normal or slightly pale. 

Reaction. — Acid. 

Specific Gravity. — This varies inversely as the quantity 
of urine, but will usually be found to vary between 10 12 
and 1 01 8. 

Coloring-matters. — All somewhat diminished except 
the indoxyl, which is generally increased. 

Normal Solids. — The absolute solids are somewhat 
diminished, although not markedly. The total quantity of 
urea eliminated by an average-sized adult will be about nor- 
mal, or it may be higher than normal, especially if the indi- 
vidual is having a liberal nitrogenous diet. Relatively, they 
are nearly normal or somewhat diminished, depending on the 
dilution of the urine. The percentage of urea will probably 
be found to be not far from 1.5 per cent. 

Albumin. — This varies between the slightest possible trace 
and a trace. It is at this time that the presence of albumin 
is sometimes overlooked, because of the failure to detect 
the slightest possible traces. (See Detection of Albumin.) 
The author's experience leads him to believe that albumin is 
always present in the urine of chronic interstitial nephritis, 
even in the early stages. 

Sediment. — This is usually very slight in quantity and 
requires very careful sedimentation in order to be able to 
obtain a satisfactory preparation for examination. Often- 
times it is necessary to centrifugalize the urine in order to 
obtain the best results from the microscopic examination. 



CHRONIC INTERSTITIAL NEPHRITIS. 311 

It will be found to consist of an occasional hyaline and finely 
granular cast. No excess of renal cells and, unless com- 
plicated, no blood or fat are present. 

In this stage the diagnosis of chronic interstitial nephritis 
from the urine alone is usually extremely difficult, but when 
combined with the clinical history and physical examination, 
it becomes less difficult, although often doubtful until the 
case has been carefully watched for some months. 

SECOND OR ADVANCED STAGE, 

The patient at this time usually finds it necessary to dis- 
continue business, because of lack of strength, habitual 
headache, more or less marked gastric disturbance, and 
perhaps other more serious symptoms ; in other words, the 
disease is at its height, and the patient requires almost con- 
stant attention. 

Character of the Urine. — Quantity. — This gradually 
but steadily increases from 2000 to 3000 or 4000 c.c. 
Rarely, it may go as high as 6000 c.c. in twenty-four hours. 

Color. — Pale and sometimes almost colorless. 

Reaction — Faintly acid. 

Specific Gravity. — This has fallen from 1012 or 1015 
to loio or lower. 

Normal Solids. — Absolutely, much diminished. Occa- 
sionally, if the disease is not very far advanced and the 
patient is having the best of care and can take a moderately 
nitrogenous diet, the urea may be nearly or quite normal, 
but this does not continue for a very long time. Relatively, 
much diminished. 

Coloring-matters. — These are all diminished, except 
the indoxyl, which is often normal or increased. 

Albumin. — This has increased, and usually varies be- 
tween a trace and ^ of i per cent. It may rarely reach 
y^ of I per cent. 

Sediment. — This is much the same as in the early stage, 
except that the casts are more numerous and usually more 
granular. The renal cells, which are only few in number, 
will be found to be quite granular. Oftentimes the abnor- 
mally formed renal elements are found with some difficulty, 
since the amount of sediment is so slight. As in the early 
stage, the urine may require centrifugalization in order to ob- 
tain a satisfactory sediment for examination. 



312 DISTURBANCES AND DISEASES OF THE KIDNEYS. 

THIRD OR LATE STAGE. 

This is at a time when the disease has advanced to a late 
stage, and the patient is more or less uremic — i. e., suffering 
from intense headache, nausea, vomiting, and often convul- 
sions. General weakness is marked. Dyspnea is often a 
prominent symptom. There is considerable vertigo and 
disturbance of vision — the so-called albuminuric retinitis. 
There may be some edema of the feet at this time, due to 
an uncompensated heart. 

Character of the Urine. — Quantity. — This has gradu- 
ally fallen from the large quantity to about 15.00 c.c. The 
quantity of urine passed at night is usually greater than that 
passed during the day. 

Color. — Very pale (watery). 

Reaction. — Faintly acid. 

Specific Gravity. — Usually between 1005 ^-^d loio ; 
even when the twenty-four-hour quantity of urine is much 
below the normal — e.g., with a quantity of 500 c.c. the 
specific gravity may be as low as 1005. 

Normal Solids. — Both absolutely and relatively much 
diminished. 

Albumin. — Usually, a distinct trace ; rarely, th.Q slightest 
possible trace. It may, on the other hand, reach as high as 
J{ of I per cent. 

Sediment. — This is still slight in quantity, and consists 
of numerous (or many) hyaline, finely and coarsely granu- 
lar, and a few waxy casts. Most of the renal cells will be 
found to be very granular. No fat nor blood unless com- 
plicated. Often in the late stage a few abnormal blood 
globules will be found. It, therefore, may be difficult from 
the urine alone and without a previous knowledge of the 
case to make a diagnosis of a primary renal disease, espe- 
cially if the quantity of urine is small and the waxy casts 
are stained by the blood so as to resemble fibrinous casts. 
The blood may be due to a slight acute exacerbation, or it 
may be the result of either a circumscribed acute nephritis or 
a more or less general active hyperemia. If the disease is 
the result of some active irritant (lead or arsenic), blood may 
be found in the sediment in all stages of the disease. 

Prominent Symptoms. — Owing to the latency of the 
disease, symptoms are frequently not noticed until the 
occurrence of one of the serious or fatal complications. 



CHRONIC INTERSTITIAL NEPHRITIS. 313 

Even an advanced grade of chronic interstitial nephritis may 
be compatible with great mental and bodily activity. There 
may have been no symptoms whatever to suggest to the 
patient the existence of a serious disease. In other cases 
the general health is greatly disturbed. The patient com- 
plains of lassitude, sleeplessness, has to arise two or three 
times at night to micturate, the digestion is disordered, and 
there are complaints of headache, failing vision, and shortness 
of breath on exertion. The pulse is usually hard, the tension 
increased, and the vessel-wall, as a rule, thickened. Hyper- 
trophy of the left side of the heart occurs, to overcome the 
resistance offered in the arteries ; and in many cases a sys- 
tolic murmur develops at the apex, probably as a result of 
relative insufficiency. Bronchitis is a frequent accompani- 
ment, especially in winter. Sudden attacks of oppressed 
breathing, particularly at night, are not infrequent. Cheyne- 
Stokes breathing may be present, most commonly toward 
the close, but the patient may be walking about and even 
attending to business. Dyspepsia and loss of appetite are 
common ; in fact, severe vomiting may be the first symptom. 
Severe and fatal diarrhea may develop ; the breath is often 
heavy and urinous. Headache is frequently an early and 
persistent feature of chronic interstitial nephritis. Hemor- 
rhages may take place into the meninges or the cerebrum ; 
such are usually associated with marked changes in the 
walls of the vessels. Disorders of vision maybe one of the 
first symptoms of the disease, and the oculist may be the 
first to make the diagnosis of a chronic form of renal 
disease. Ringing in the ears, with dizziness, is not un- 
commion. 

Edema, except very slight swelling of the ankles, is very 
uncommon in chronic interstitial nephritis until late in the 
disease, when it is probably due to an uncompensated 
heart. The skin is often dry and pale. Epistaxis may 
occur and prove serious. Uremic symptoms, some of 
which have been mentioned, are common in the advanced 
stage of the disease. Uremic convulsions may be frequent 
and severe. 

Duration. — A chronic interstitial nephritis is usually in 
progress for many years — from ten to thirty, or a longer 
time. It is most common in middle life, and if discovered 
early and the source determined, by good care the patient 
may have fair health for many years. 



314 DISTURBANCES AND DISEASES OF THE KIDNEYS. 

Prognosis. — The prognosis is very unfavorable, although, 
as has been stated, if the disease is discovered during its 
early stages, the patient may live many years. Occasion- 
ally, the patient dies of some intercurrent disease such as 
pneumonia, or, perhaps more commonly, cerebral hemor- 
rhage because of the diseased arteries. Frequently, a sud- 
den attack of uremia results fatally. The appearance of 
waxy casts usually indicates that the fatal termination will 
occur within one year, and often within six months. 

Clinically, an uncomplicated case of chronic interstitial 
nephritis — that is, one that does not present some evidence 
of a slight parenchymatous change (presence of fat) — is 
quite uncommon, it being the rule to find rarely a fat 
globule adherent to an occasional cast. 

Differential Diagnosis. — The diagnosis of an early stage 
of clironic interstitial nephritis from the urine alone is often 
difficult, owing to the fact that the urine is so slightly 
altered from the normal. It is at this time that a very care- 
ful consideration of the clinical history and the physical 
examination are of infinite importance. It is needless to say 
that an early recognition of this form of nephritis is very 
important, for if it is the result of some chronic irritation, as 
by lead or uric acid, the same should be recognized and the 
irritant removed as early as possible. 

The so-called ''cardiac and renal " cases are worthy of 
consideration here because of the differential diagnosis 
between a chronic ijtterstitial nephritis and passive hyperemia. 
The latter condition is sometimes superimposed on the 
former because of an uncompensated heart. From the 
urine alone it is often impossible to decide which con- 
dition is the more prominent. A very small twenty-four- 
hour quantity of urine, a comparatively small amount of 
albumin (trace), and the presence of marked edema are all 
against a chronic nephritis. On the other hand, if the sedi- 
ment contains waxy casts, or casts from extensively denuded 
tubules, very granular renal cells, and, clinically, a high 
tension pulse, and other evidences of increased blood pres- 
sure, the condition may be a chronic interstitial nephritis in 
a late stage, and at a time in the disease when the edema is 
the direct result of the secondary disease of the heart. It 
is sometimes necessary to watch the effect of treatment by 
digitalis or other drugs that act chiefly on the diseased 
heart before deciding as to the probabiHty of an underlying 



SENILE INTERSTITIAL NEPHRITIS. 315 

chronic interstitial nephritis. If the original abnormal 
features of the urine were the results of a passive congestion, 
such abnormalities will usually largely disappear as the con- 
dition of the heart improves by treatment. 

It is often difficult, if not impossible, to distinguish between 
an active hyperemia attended zvitJi low metabolism, and a late 
stage of a chronic interstitial nephritis attended with a very 
slight acute process and without the presence of waxy casts 
in the sediment. About five years ago the author examined 
the urine of a man, aged seventy, in which the urinary picture 
was quite typical of an active hyperemia. Uremic coma 
developed two days later and death followed. At the 
autopsy very small, red, granular kidneys were found, 
indicative of a marked chronic interstitial nephritis. Of 
course, in such cases, a knowledge of the clinical history 
and the physical examination are of the greatest importance. 

The usual prominent signs and symptoms of a chronic 
nephritis will, in most cases, serve to establish the diag- 
nosis. 

SENILE INTERSTITIAL NEPHRITIS. 

Synonym. — Senile atrophy of the kidneys. 

This form of disease usually occurs in persons after the 
age of from fifty to sixty ; but the disease is not necessarily 
present in every elderly person. It is usually a part of the 
general degeneration of the blood-vessels and sometimes a 
part of a general arteriosclerosis. 

In the senile kidney the chief lesions are those due to 
disease of the vessels. These vascular lesions are accom- 
panied by impairment in the power of regeneration. Pre- 
vious lesions of the kidney, even though slight in character, 
may gradually make their influence felt in impairing the 
resistance of the tissue. The epithelial lesions may consist 
chiefly in atrophy. Microscopically, the kidney is usually 
more or less injected and atrophied. On microscopic exam- 
ination the epithelium of the tubules is degenerated, small, 
and atrophic. The formation of yellow pigment in the 
atrophic epithelium is frequently seen. There is some gen- 
eral increase in the connective tissue, but this is chiefly 
marked close beneath the capsules, and may extend from 
here in lines into the cortex (Councilman). 

Character of the Urine. — The urine does not bear the 
usual characteristics of the typical chronic interstitial 



316 DISTURBANCES AND DISEASES OF THE KIDNEYS. 

nephritis, but has more the appearance of a passive 
hyperemia. 

The quantity is generally not far from 1 500 c.c, and may 
even be considerably below the normal. 

The albumin is, ordinarily, from the slightest possible trace 
to a trace. 

The normal solids are absolutely diminished, but no more 
than would be expected in a person of advanced years 
when the metabolism is decidedly low. Relatively, they are 
about normal. 

The sedime?it has practically the same appearance as in 
the early form of chronic interstitial nephritis — an occa- 
sional hyaline and granular cast and granular renal cell. 

It may be impossible from the urine alone and without a 
knowledge of the case to make a positive diagnosis of a 
senile interstitial nephritis. 

CHRONIC DIFFUSE NEPHRITIS. 

Synonym. — Chronic diffuse nephritis with exudation. 

Chronic diffuse nephritis is undoubtedly one of the most 
common of the chronic diseases of the kidney. 

From a clinical point of view, this form of disease par- 
takes essentially of two pathologic conditions : (i) An i?iter- 
stitial element, which is generally very prominent and shown 
by the increased twenty-four-hour quantity, pale color, low 
specific gravity, increased indoxyl, and relatively and abso- 
lutely diminished normal solids ; (2) a parencJiymatous ele- 
'}nent, shown by the comparatively high percentage of albu- 
min and the presence of fatty renal elements (fatty casts, 
fatty renal cells, etc.) in the sediment. Usually, the inter- 
stitial element is predominant, hence the characteristic 
features of the disease in a general way resemble those of a 
chronic interstitial nephritis. 

Pathologically, the morbid processes in the kidney may 
consist of any one, or a combination of any, of the following 
conditions : Chronic glomertdar nephritis, chronic arterio- 
sclerotic nephritis, chronic degenerative and interstitial neph- 
ritis. 

In chronic glomerular nephritis the essential lesions are 
in the glomeruli, and consist of extensive hyaline degenera- 
tion of tufts and of entire glomeruli, and obliteration of 
capillaries. Every transition may be seen between these 



CHRONIC DIFFUSE NEPHRITIS. 317 

glomerular lesions and those in the subacute form of neph- 
ritis. There may be some increase in the capsular epithe- 
lium and connective-tissue formation within the capsule. 
The tubular epithelium shows extensive degeneration and 
destruction. Entire tubules are destroyed, often being rep- 
resented by the thickened irregular membrana propria. 
There is a general and diffuse increase of the connective 
tissue affecting almost equally all parts of the kidney. This 
condition is usually found as an independent affection, or it 
may be combined with acute infections of various sorts, 
when there is often a history that points to a previous acute 
or subacute affection. The kidney may be slightly larger 
than normal, of normal size, or considerably smaller than 
normal. The capsule is often adherent, the surface even, not 
granular, and pale. On section, the cortex varies in width ; 
it may be quite small, opaque, whitish, the markings obscure, 
the glomeruli not visible nor pale, and the consistence of the 
tissue greatly increased (Councilman). 

(For the pathologic description of chronic arteriosclerotic 
nephritis and of chronic degenerative and interstitial neph- 
ritis, see pp. 307, 308.) 

Causes. — The causes of a chronic diffuse nephritis are, 
in some instances, probably the same as those of chronic 
interstitial nephritis. The disease sometimes follows an 
acute nephritis in which the stage of convalescence has been 
prolonged for many months or years. The author has 
met with a few cases in which a chronic diffuse nephritis 
followed an acute nephritis of pregnancy. 

Prominent Symptoms. — In the majority of cases of 
chronic diffuse nephritis the symptoms are, in many respects, 
the same as in chronic interstitial nephritis. But in this dis- 
ease there is constantly more or less edema, which is usu- 
ally slight during the early stages, becoming more marked 
as the disease advances, when general dropsy may be 
extreme. There is usually gastric disturbance and fre- 
quency of micturition, accompanied by an increase in the 
daily quantity. Circulatory disturbances are more or less 
marked, especially when the disease forms a part of a 
general arteriosclerosis. Anemia, a pasty appearance of 
the skin, emaciation, and visual disorders are not uncom- 
mon. Uremic symptoms are frequently met with, especial- 
ly in advanced cases, or as the result of acute exacerba- 
tions. 



318 DISTURBANCES AND DISEASES OF THE KIDNEYS. 

The characteristics of the urine of the average advanced 
case of chronic diffuse nephritis are as follows : 

Character of the Urine. — Quantity. — The average 
quantity is about 2000 c.c. It may be considerably 
higher — 3000 c.c. — or lower, — 1500 c.c, — and it may oc- 
casionally be below the normal, but only temporarily. The 
quantity of urine at night often exceeds that of the day. 

Color. — Pale and sometimes greenish. 

Specific Gravity. — Average loio to 1015. If the 
twenty-four-hour quantity is unusually high, the specific 
gravity may be from 1004 to 1008. 

Normal Solids. — Absolutely, diminished and sometimes 
to a marked degree ; relatively, much diminished. The 
indoxyl is generally normal or increased. 

Albumin. — This varies between a large trace and ^ of i 
per cent., but the average is usually between y^ and y^ of 
I per cent. The quantity of albumin is much larger than 
in chronic interstitial nephritis and smaller than in subacute 
glomerular nephritis. 

Sediment. — This is generally slight in quantity, and con- 
sists of numerous hyaline and granular casts, mostly with 
fat adherent ; an occasional (or few) fatty cast ; numerous 
renal cells, most of which are fatty, and a few compound 
granule cells. No blood is seen unless complicated. If the 
disease is far advanced, a few waxy casts will be found ; 
occasionally, they are present in large numbers. When 
waxy casts appear in the sediment, the twenty-four-hour 
quantity of urine will usually be less than normal. 

In case the parenchymatous eleuient predominates the 
quantity of urine will be not far from the normal (1500 
c.c), the specific gravity and quantity of albumin will be 
correspondingly high, and the amount of fat in the sediment 
will be greater than indicated above. If, on the other hand, 
the interstitial element predominates, the quantity of urine 
will be large (2500 to 3000 c.c), the specific gravity and 
quantity of albumin correspondingly low, and the amount 
of fat comparatively small. 

Differential Diagnosis. — In the diagnosis of chronic 
diffuse nephritis special attention should be paid to the 
twenty-four-hour quantity of urine, which, if permanently 
increased, will usually serve to distinguish it from a subacute 
glomerular nephritis. In some instances of chronic diffuse 
nephritis, notably following an acute exacerbation while the 



AMYLOID INFILTRATION. 319 

dropsy is still marked, the total quantity of urine is often 
less than normal, the quantity of albumin is very large, and 
the amount of fat is excessive. Under these circumstances 
it is usually impossible from the urine alone to distinguish 
the condition from a subacute glomerular nephritis, without 
watching the urine for a considerable period. It is often 
impossible to differentiate between a chronic diffuse nephritis 
near death, and a subacute glomerular nephritis also near 
death. 

A chronic diffuse nephritis is distinguished from an un- 
complicated chronic interstitial nephritis by the presence of 
fat in the sediment, the comparatively high quantity of 
albumin, and, upon physical examination, the presence of 
edema in the former disease. 

The duration of chronic diffuse nephritis will depend 
largely on whether the interstitial or the parenchymatous 
element predominates. If the former, the patient may live 
from ten to fifteen years, providing he has the best of care ; 
on the other hand, if the parenchymatous element is pre- 
dominant, the duration of life is usually between five and 
ten years. As in subacute glomerular nephritis, acute ex- 
acerbations are very likely to occur, and if they are very 
numerous, the duration of life may not exceed from five to 
eight years, and often death occurs within a much shorter 
period. 

The prognosis is, in most cases, grave. The appearance 
of waxy casts in the sediment is an unfavorable sign ; death 
will probably occur within one year. 

AMYLOID INFILTRATION. 

Synonyms. — Lardaceous kidney ; waxy degeneration ; 
chronic depurative disease of the kidneys. 

Amyloid infiltration is a disease that is not confined alone 
to the kidneys. The lesions are usually prominent in other 
organs of the body as well — notably the liver and spleen. 

In amyloid infiltration, as the name implies, the character- 
istic lesion is the amyloid infiltration about the blood-vessels ; 
consequently, the portion of the kidney that is most seriously 
affected is the glomerulus. There may be small masses of 
amyloid along the vascular loops, or the entire glomerulus 
may be converted into a glassy, homogeneous mass, the 
result of the deposit of the amyloid material. Usually, 



320 DISTURBANCES AND DISEASES OF THE KIDNEYS. 

some of the glomeruli are only moderately affected, hence 
the functions of the kidneys are maintained for some 
period. 

The amyloid material is stained a mahogany-brown color 
by iodine, whereas the unaffected tissue takes a delicate 
yellow stain ; and a rose-red color by methyl-violet, the 
undiseased tissue being stained blue. 

Causes. — Amyloid infiltration is often an accompaniment 
of syphilis, phthisis, tubercular disease of the joints, chronic 
suppuration of the bones, and chronic wasting diseases. The 
exact reason for amyloid infiltration in these conditions is 
not known. 

Prominent Symptoms. — The features of the urine alone 
may not definitely indicate the presence of this disease. 
Usually, the associated conditions (syphilis, tuberculosis, 
etc.) give hints as to the nature of the process. The liver 
and spleen are usually enlarged. Diarrhea is a common 
symptom. Increased arterial tension and cardiac hyper- 
trophy are not usually present, except in those cases in 
which amyloid infiltration occurs in the secondaiy con- 
tracted kidney. Under these circumstances there may be 
uremia and retinal changes, which, as a rule, are not met 
with in uncomplicated amyloid infiltration. Frequency of 
micturition and the elimination of a large quantity of urine 
in twenty-four hours are often important and early signs. 
It is essential that the clinical history, the physical examin- 
ation, and the urine should receive equal weight in the diag- 
nosis of amyloid infiltration ; it rarely happens that the urine 
alone affords sufficient data for an accurate diagnosis. 

Character of the Urine. — The urine of a well-advanced 
case of amyloid infiltration is as follows : 

Quantity. — Usually, above 1500 c.c. ; generally, between 
2000 and 4000 c.c. The quantity of the day urine usually 
exceeds that of the night. Like the other chronic affec- 
tions of the kidneys, the quantity generally falls to normal 
or below the normal a short time before death. 

Color. — Generally, very pale ; the urine often has a 
greenish tint. 

Specific Gravity. — This is below the normal ; it is usu- 
ally found to vary between 10 12 and 10 1 8. 

Normal Solids. — Absolutely, normal or slightly dimin- 
ished, but dependent upon the metabolism. Relatively, 
much diminished, especially if the Quantity of urine be very 



AMYLOID INFILTRATION. 321 

large. The probable explanation of the normal quantity of 
solids in the urine is the fact that the parenchyma or secret- 
ing structure of the kidney does not become involved until 
late in the disease, the principal pathologic changes being 
about the blood-vessels. Absolutely, the indoxyl may be 
increased, but it is usually diminished. 

Albumin. — In an uncomplicated case the quantity of 
albumin varies between a trace and y^ of i per cent. ; only 
rarely does it exceed ^ of i per cent. On the other hand 
it may be less than a trace, particularly if the quantity of 
urine is in the neighborhood of 4000 c.c. 

Sediment. — This is generally very slight in amount, and 
consists of a few hyaline, granular, and occasional (or few) 
waxy casts ; rarely, a renal cell. No fat nor blood, unless 
complicated. 

The waxy casts appear rather early in this disease, much 
sooner than in the other chronic diseases of the kidney. 
The question has often arisen as to whether the waxy casts 
found in amyloid disease were cylinders of amyloid material 
or of the same composition as those found near the end of 
other chronic affections of the kidney ? The queiy still 
remains unsettled, for the reason that it is very difficult to 
satisfactorily stain the waxy casts by the stains ordinarily 
used for the detection of amyloid material. If the suspected 
sediment is first washed several times by decantation with a 
dilute solution of glycerine, and methyl-violet added, some 
of the casts (both waxy and hyaline) will be found to have 
a slight reddish tint. Further experiments are, however, 
necessary before any definite conclusions can be drawn from 
the use of stains. 

Amyloid disease of the kidney is ^^ery apt to be compli- 
cated by parenchymatous degeneration ; such changes are 
probably secondary to the extensive deposit of amyloid 
material in the glomeruli and the resulting interference with 
the nutrition of the renal epithelium. Sometimes this 
parenchymatous change is very marked, so that the urine 
will have the characteristics of chronic diffuse nephritis ; or 
it may predominate to such an extent that the urine will 
resemble one of subacute glomerular nephritis, the evi- 
dences of amyloid being thereby obscured. 

Differential Diagnosis. — In the diagnosis between an 
imcomplicated amyloid infiltration and a chronic interstitial 
nephritis \h^ enlarged liver and spleen, an absence of increased 



322 DISTURBANCES AND DISEASES OF THE KIDNEYS. 

arterial tension and cardiac hypertrophy, and the history' 
of syphiHs, tuberculosis, etc., will usually indicate amyloid 
disease. From the urine alone it is impossible to distin- 
guish with certainty between these two conditions. It 
should be said, however, that in amyloid infiltration the 
total solids and the total quantity of urea are usually 
higher than in chronic interstitial nephritis, but such a rule 
is by no means invariable, since amyloid disease is often ac- 
companied by a chronic disease that very much diminishes 
the metabolism. 

As previously stated, in considering the diagnosis of this 
disease the physical examination and clinical history should 
always be carefully weighed along with the characteristics 
of the urine. 

The duration of this disease is largely dependent on the 
cause. As a rule, it extends over a period of several years 
—from ten to fifteen ; sometimes a longer, and occasionally 
a much shorter, time. 

The prognosis depends rather on the condition with 
which this renal affection is associated. As a rule, it is 
grave. 



CHAPTER IX. 



DISEASES OF THE KIDNEYS (CONTINUED). 

TUBERCULOSIS OF THE KIDNEYS. 

Primary tuberculosis of the kidneys is not very rare. It 
occurs in two distinct forms — viz., local caseating tuberculo- 
sis and acute miliary tuberculosis. The latter form is always 
associated with tuberculosis in other parts of the body, such 
as phthisis pulmonalis and tubercular meningitis. This 
form rarely gives rise to distinct urinary symptoms. Local 
caseating tuberculosis, on the other hand, usually results in 
urinary symptoms to a marked degree, and it is this form 
that deserves special consideration in this connection. 

The substance of the kidney may contain only a few, or 
there may be a large number of, tubercular nodules. The 
process very soon involves the pelvis of the kidney, and in a 
majority of the cases not only the pelvis but the ureter as 
well, and sometimes the bladder and prostate. It may be 
difficult to say in advanced cases whether the disease has 
started in the bladder, prostate, or seminal vesicles, and crept 
up the ureters, or whether it started in the kidneys and pro- 
ceeded downward. Osier believes that in the majority of cases 
the latter is true, and the infection is through the blood. One 
kidney alone may be involved, and the disease creeps down 
the ureter and may involve the mucous membrane of the 
bladder to a greater or less extent. The process is com- 
mon in the middle period of life, but it may occur in the 
extremes of age. It is more frequent in males than in 
females. 

Prominent Symptoms. — The symptoms are usually 
those of chronic pyelitis. The urine may be purulent for 
years, and there may be little or no distress. Even before 
the bladder becomes involved micturition is often frequent, 
and many instances are mistaken for cystitis. The condi- 

323 



324 DISEASES OF THE KIDNEYS. 

tion may be in progress for many years without marked 
impairment of health. In cases in which the disease be- 
comes advanced and both organs are affected, constitutional 
symptoms are more marked. General tuberculosis is com- 
mon. Intermittent hematuria is of frequent occurrence, 
denoting ulcerative changes in the mucous membrane of the 
tubules of the kidney. 

Physical examination may detect special tenderness on 
one side, or the kidney may be palpable in front on deep 
pressure ; but a tuberculous kidney seldom causes a large 
tumor. Occasionally, the ureter becomes occluded and 
pyonephrosis results ; but this is rare in comparison with its 
frequency in calculous pyelitis. 

Character of the Urine. — Early in tuberculosis of the 
kidney the urine is only slightly altered from the normal. 
There may be the slightest trace of albumin, and the sedi- 
ment may contain only a very few leucocytes and an occa- 
sional blood globule. When, however, the disease becomes 
more advanced and ulcerative changes have begun, the 
urine will usually have the following characteristics : 

Quantity. — The total quantity of urine for twenty-four 
hours is generally increased, although it may be normal or 
diminished. 

Color. — Pale. The urine is usually more or less turbid, 
due to the pus, blood, etc., in suspension. 

Reaction. — Generally acid, except when the urine con- 
tains an abundance of blood, when it may be faintly acid or 
alkaline. 

Specific Gravity. — Usually below the normal — loio to 
10 1 5, or thereabouts. 

Normal Solids. — Both relatively and absolutely, dimin- 
ished. If there is general advanced tuberculosis, the solids 
will be absolutely very low. 

Albumin. — The quantity of albumin is dependent, in the 
first place, on the amount of destruction of the kidney, and, 
secondly, on the amount of pus and blood present. If the 
disintegration of the renal tissue is marked, the albumin is 
usually high, approximating from i^ to i^ of i per cent. 
If, on the other hand, the tubercular process is localized and 
not extensive, the amount of albumin may not exceed a 
slight trace, or trace. 

Sediment. — Abundant. Chiefly pus, which is usually 
free, but may be more or less clumped ; the pus may be 



TUBERCULOSIS OF THE KIDNEYS. 325 

markedly degenerated. Many small round cells, some of 
which are usually fatty. Hyaline and granular casts, some 
of larger diameter, are usually present, but they may be so 
obscured by the pus as to escape detection. Blood is gen- 
erally present, but sometimes in small amount ; it may, 
however, be very abundant, intermittent hematuria being a 
common symptom of this disease. The sediment also con- 
tains tubercle bacilli. 

To distinguish the condition from a calculous pyelitis is 
often difficult. Hemorrhage may be present in both condi- 
tions, though not nearly so frequently in the tuberculous 
disease. The diagnosis rests on three points : (i) The 
detection of some focus of tuberculosis, as in the testes ; (2) 
the presence of tubercle bacilli in the sediment ; and (3) the 
use of tuberculin. In women the kidney involved is now 
easily determined by catheterizing the ureters after the plan 
introduced by Kelly, of Baltimore. Dr. Edw. Reynolds, 
has recently reported a case of early tuberculosis of the 
kidney,^ in which the author had the opportunity of 
making a careful study of the urine, and in which cathet- 
erization of the ureters led to the location of the disease. 

Detection of Tubercle Bacilli in the Urinary Sediment. 

Either centrifugalize the urine or allow the sediment to 
settle by gravity ; decant the supernatant urine, and wash 
twice by decantation with distilled water. After the second 
washing, centrifugalize. The sediment is then taken up by 
means of a pipette and placed on from four to eight cover- 
glasses, which have been carefully cleansed in nitric acid 
and then in alcohol. Care should be exercised not to get 
too much sediment on the cover-glasses, for the layer may, 
after drying, be too thick, especially if there is much pus in 
the sediment. These cover-glass preparations are then 
dried by placing them on an iron or copper plate, under 
which is placed a very small flame (about y^ of an inch 
in height will suffice), the main object being to get very 
gentle heat so that the specimens will be dried slowly 
and without being charred. Stain the dried preparations 
with either carbol-fuchsin (Ziehl-Neelson) or aniline water 
and fuchsin (Koch-Ehrlich) in the usual manner. Decolor- 
ize in 20 per cent, nitric acid, wash in water, and, finally, still 

1" Johns Hopkins Bulletin," Nov., 1898, p. 253. 



326 DISEASES OF THE KIDNEYS. 

further decolorize in yo per cent, alcohol for at least ten 
minutes. Then stain with an aqueous solution of methylene- 
blue, mount, and examine. 

It is very important that the preparations should be 
thoroughly decolorized in alcohol in order to be able to 
distinguish between tubercle bacilli and smegma bacilli ; 
the latter being quite readily decolorized by this means, 
while the former are not affected. A very close resem- 
blance exists between these two organisms. At times the 
smegma bacillus appears thicker than the tubercle bacillus, 
and sometimes the ends have a clubbed appearance, but 
this is not true in all instances ; consequently, the data thus 
far at hand are of no differential importance. Smegma 
bacilli are not uncommon in the urine of both male and 
female, particularly in the urine of those who are not 
cleanly. It is obvious that special care should be taken in 
procuring a specimen that is to be examined for tubercle 
bacilli. Since in those individuals who are not cleanly the 
smegma collect about the genitalia, it is essential that these 
parts be thoroughly cleansed before the urine is voided. A 
still better procedure is to procure a catheter specimen, if 
possible. Attention to these details contributes materially 
to a satisfactory result of the examination. 

Tubercle bacilli in the urine are usually arranged in 
groups (Plate 9), although they may occur singly. They 
may be present in large numbers and easily found ; on the 
other hand, they may be rare and escape detection even after 
prolonged examination. The fact that tubercle bacilli can not 
be found in a urinary sediment does not, then, prove their 
absence. In all suspicious cases a portion of the sediment 
(j4 to I c.c.) should be injected into the peritoneal cavity 
of a guinea-pig. If the bacilli are present, the animal will 
develop tuberculosis in from six to eight weeks ; if not 
present, the animal will not be affected by the inoculation. 
This constitutes the safest method for the detection of 
tubercle bacilli in urine. 



RENAL CALCULUS. 

Calculi may originate in the secreting structure of the 
kidney, — usually in the tubules, — forming cavities for their 
location in the parenchyma of the organ. 

Renal calculus is usually unilateral, though there are 



Plate 9 



\J^ 









^) f 



m 



w 



Tubercle Bacilli in Urinary Sediment ; X ^oo- (Personal 
Observation.) 



RENAL CALCULUS. 327 

many exceptions to this rule. The calculus, when large, is 
usually single, the smaller ones being more apt to be 
multiple. 

Renal calculus occurs at all ages, including intra-uterine 
life. It is, however, most common before fifteen, and after 
fifty, years of age. In young people and children calculi 
are most frequent among the poor, while the condition in 
advancing life is most common in people in comfortable cir- 
cumstances and of luxurious habits. As a rule, the calculi 
in infancy are composed of ammonium urate ; those in 
young adults, uric acid ; those after fifty years of age are 
made up of either uric acid or calcium oxalate. 

Prominent Symptoms. — These consist of dull aching 
pain situated deeply in the loin, usually unilateral, and 
often radiating along the ureter toward the testicle or labia, 
down the thigh, and sometimes extending as far as the 
foot. The pain may be sharp and lancinating at times. 
When a stone enters the ureter, intensely severe paroxysms 
of pain (renal colic) are usually experienced, lasting a few 
hours and then suddenly subsiding. The ordinary pain of 
renal calculus is nearly always increased by exercise — walk- 
ing or riding. There is often tenderness upon deep pressure 
anteriorly, especially if the calculus has excited much in- 
flammation. Gastric disturbances are common, including 
nausea, vomiting, and periods of more or less disordered 
digestion, hyperacidity, flatulence, etc. 

Character of the Urine. — The urine is usually highly 
concentrated, of high color, high specific gravity, and sharply 
acid reaction. Sometimes it has a decided smoky color, 
because of the presence of altered blood pigment. Rela- 
tively, the solids are generally increased ; absolutely, about 
normal, providing the patient is in good general condition ; 
as a rule, the normal solids will depend upon the meta- 
bolism. 

The amount of albumin depends on the extent of the 
irritation and the quantity of blood. 

The sediment is usually that of an active hyperemia or 
irritation of the kidneys. It is not uncommon to find crys- 
tals or microscopic concretions of the same substance as the 
calculus that is being formed in the kidney. There maybe 
a considerable quantity of blood, which is usually abnormal 
in character, providing the hemorrhage is not abundant ; if 
profuse, there is generally more or less normal blood. The 



328 DISEASES OF THE KIDNEYS. 

sediment may or may not contain pus. It is more common 
perhaps to find only a few leucocytes rather than an abun- 
dance of pus. If much pus is present, it is probable that 
either an abscess of the kidney or a chronic pyelitis has been 
produced by the stone. 

Renal calculi usually consist of either uric acid or urates, 
calcium oxalate, or cystin. Occasionally, the calculus is 
the result of a deposit of phosphates in the kidney. Such 
a deposition is always secondary to an extension upward 
from the bladder or pelvis of the kidney. In case of a 
phosphatic calculus in the kidney the urine is usually pale 
in color, with an alkaline reaction, and an abundant deposit 
of phosphates in the urinary sediment. 

ABSCESS OF THE KIDNEY. 

Abscess of the kidney is usually due either to injury of 
the organ, to an encysted concretion that sets up a marked 
irritation in some portion of the kidney, or to tubercular 
disease of the organ. 

The condition is accompanied by the usual symptoms of 
an abscess in any part of the body — viz., fever, localized 
pain, cachexia, marked languor, nausea and vomiting, etc. 
On the affected side there may be a distinct tumor, which, 
on manipulation, is found to be extremely tender ; again, the 
condition may exist without tumor. 

The abscess usually ruptures into the pelvis of the kidney 
or into the renal tubules, and the urine that was free from 
pus will suddenly contain a large amount of it. 

Character of the Urine. — The urine generally has the 
characteristics of a fever urine — high color, high specific 
gravity, strongly acid reaction, and containing a very slight 
trace or a trace of albumin. The sediment usually has the 
appearance of one of active hyperemia, which may be mild 
or severe, according to the extent of the inflammatory 
process (circumscribed acute nephritis) about the abscess, 
and the degree of disturbance that is invariably set up as a 
result of the elimination of toxines by the healthy kidney. 
As soon as the abscess evacuates into the urinary tract, 
the sediment, which is abundant and usually of a greenish 
color, contains an abundance of degenerated pus, many 
small round cells, usually a few compound granule cells, 
and more or less blood. There is frequently hematuria fol- 



RENAL EMBOLISM. 329 

lowing the evacuation of the abscess, especially if any of 
the renal blood-vessels have been ruptured. This hem- 
orrhage may be slight and of short duration if due to 
injur>^ of the capillaries, and may be extensive and per- 
sistent if one or more of the larger vessels have been 
ruptured. 

The sudden appearance of a large amount of blood and 
pus in a urine that has previously been clear and free from 
these elements is strongly suggestive of abscess of the 
kidney, especially when taken in conjunction with the 
clinical history and symptoms. A diagnosis of this con- 
dition can not be made from the urine alone previous to the 
rupture of the abscess and without a clinical knowledge of 
the case. 

The prognosis is usually grave when the disease is of 
tubercular origin. When it is due to trauma or to an 
encysted concretion, the prognosis is often good if an early 
diagnosis is made. Occasionally, recovery follows drainage 
of the pus-sac, and in rare instances spontaneous recovery 
takes place, particularly when the destructive changes are 
only slight. In most cases of abscess of the kidney sur- 
gical interference is necessary. 



RENAL EMBOLISM. 

Renal embolism consists of an impacted thrombus that 
has formed in some part of the circulatory system, — usually 
on the valves of the heart, — and is carried by the blood 
current to the kidney, where it occludes one of the renal 
vessels. The anatomic changes resulting from renal em- 
bolism are very constant and striking, and the condition is 
quite commonly found at the autopsy, although only rarely 
recognized during life. 

Prominent Symptoms.^A previous history of endo- 
carditis is generally found. The sudden pain that usually 
accompanies the occlusion of the renal vessel may be 
severe, often followed by nausea and vomiting, and some- 
times by a state of collapse. On the other hand, the pain 
may be comparatively slight, although usually persistent 
for some time. Chills and a more or less irregular tem- 
perature are frequent accompaniments of this condition. 

Character of the Urine. — From the urine alone the 
diagnosis of a renal embolism is practically impossible. 



330 DISEASES OF THE KIDNEYS. 

The urinary changes usually begin abruptly, and the urine 
suddenly has the characteristics of one accompanying fever. 
The urine is usually much diminished in quantity, of high 
color, and high specific gravity — 1025 to 1 03 5. Rela- 
tively, the normal solids are increased ; absolutely, normal or 
slightly diminished. The quantity of albumin depends upon 
the extent of the disturbance in the neighborhood of the area 
affected by the embolus. The sediment usually has the 
characteristics of a more or less severe active hyperemia 
or a circumscribed acute nephritis, which is in progress 
around the diseased area. 



TUMORS OF THE KIDNEY. 

These are benign or malignant. Of the benign tumors, 
the most common are the fibromata ; lipomata, lymph- 
adenomata, and angiomata are constantly met with. Ade7io~ 
inata may be congenital. Malignant growths — sarcoma or 
carcinoma — may be either primary or secondary. Sarcomata 
are the more common. 

Tumors of the kidney grow rapidly and may attain a 
very large size — 12 to 30 pounds. They are often soft, 
and hemorrhages frequently occur in them. In sarcomata 
invasion of the pelvis or of the renal vein is comm-on. In 
almost all instances tumor is present. An increasing tumor 
in the anterior lumbar region, between the costal arch and 
the. crest of the ilium, is always suggestive of renal tumor. 
The tumors are usually fixed, although they may be mov- 
able ; they are frequently lobulated. 

Prominent Symptoms. — Hematuria. — This may be the 
first indication. The blood is fluid or clotted ; sometimes 
a blood-clot is passed having the appearance of a cast of 
the ureter. 

Progressive Emaciation. — Loss of flesh is usually marked 
and advances rapidly. 

Pain. — This is generally present, and of a dull aching 
character, situated in the flank and radiating down the thigh. 
The pressure of the tumor often causes severe and alarming 
symptoms, such as edema of the feet and legs, ascites, dis- 
turbances of the stomach, various neuroses, — the result of 
pressure on the large nerve-trunks, — and anemia. There is 
often frequent micturition, which may be so marked as to indi- 
cate a disease of the bladder when only the kidney is involved. 



CYSTIC DISEASE OF THE KIDNEYS. 331 

Character of the Urine. — Perhaps the most prominent 
feature of the urine is the presence of more or less blood — 
hematuria ; occasionally, the amount of fresh blood is 
very large, but this is not true in every case. The urine 
usually shows evidence of a circumscribed inflammation or 
congestion of the kidney in the neighborhood of the new 
growth : in other words, the urine presents the picture of a 
more or less severe active hyperemia of the kidney. Pus is 
generally absent in the sediment, save in advanced cases 
attended with decided destructive changes in the kidney or 
changes in the new growth itself Under such circum- 
stances the quantity of pus is comparatively small, consider- 
ing the extent of the necrotic changes. Rarely, cancer 
elements can be recognized in the urinary sediment. Occa- 
sionally, the presence of a large number of epithelial cells 
with large and prominent nuclei and of various shapes is 
strongly suggestive of new growth, especially if the mucous 
membrane of the pelvis is involved or has become ulcerated. 
The presence in the sediment of organized elements, such as 
renal casts, renal cells, etc., is of little or no diagnostic 
value in renal cancer. 

A diagnosis of renal cancer from the urine alone is only 
of the rarest occurrence, and then only in case particles of 
the morbid growth with a distinct alveolar structure are 
discovered in the sediment ; but in malignant disease 
hmited to the parenchyma of the kidney the appearance 
of portions of the growth in the sediment is practically un- 
known. 

CYSTIC DISEASE OF THE KIDNEYS. 

Cystic disease of the kidneys is probably the result, in 
most cases, of some obstruction to the outflow of urine 
through one or more renal tubules. Three varieties of 
cysts are met with : 

1. Small cysts, seen especially in chronic interstitial neph- 
ritis, resulting from dilatation of obstructed tubules or Bow- 
man's capsule. 

2. Solitary cysts, ranging in size from a marble to an 
orange, or even larger, without evidences of other changes 
in the kidney. 

J. Congenital cystic kidneys. In this condition the kid- 
neys are represented by a conglomeration of cysts varying 
in size from a pea to a marble. The organs are greatly en- 



332 DISEASES OF THE KIDNEYS. 

larged, and together may weigh from seven to ten pounds. 
In the fetus they may attain a size sufficient to impede 
labor. Little or no renal tissue may be noticeable, although 
on microscopic examination it is seen that a considerable 
amount remains in the interspaces. 

The cystic fluid is usually clear, but it may be turbid, and 
sometimes reddish-brown or even black in color ; occasion- 
ally, it is viscid. Specific gravity is usually low. Albumin, 
blood-corpuscles, and sometimes hematoidin crystals, leuco- 
cytes, cholesterin, triple phosphates, and fat globules are 
found in the contents. Urea and uric acid are present 
only in traces. The contents of one cyst may have an 
entirely different character from those of an adjacent cyst. 

Character of the Urine. — In general the character of 
the urine is that of a chronic interstitial nephritis. In some 
instances the urine is not abnormal, especially in those cases 
in which there are no other changes in the kidney. 

The diagnosis of cystic disease of the kidney can not 
be made with certainty from the urine alone. The condi- 
tion, especially the congenital form, may exist unsuspected 
until found at the autopsy, death being the result of some 
other disease. Great enlargement of both kidneys, with 
hypertrophy of the left ventricle and increased arterial ten- 
sion, would suggest cystic disease. 

Operative interference is not justifiable. It is important 
to remember that the conglomerate cystic kidney is almost 
invariably bilateral. Osier cites an instance in w^hich one 
kidney was removed and the patient died within twenty -four 
hours from cystic disease of the other kidney. 



CHAPTER X. 

DISEASES OF THE URINARY TRACT BELOW 
THE KIDNEY PROPER^ 

The diseases of the urinary tract below the kidney 
proper have received names according to their location and 
their duration. They are, for the most part, inflammatory 
in character, and may be either acute or chronic. In a 
consideration of the urine of all such diseases, the quantity 
of albumin, the total amount of urea, and the character of 
the sediment are of special importance for purposes of 
diagnosis. 

PYELITIS. 

This is an inflammation of the mucous membrane of the 
pelvis of the kidney ; it may be either acute or chronic. 

ACUTE PYELITIS. 

An acute inflammation of the pelvis of the kidney may 
be either mild or severe, and local or general. Primary 
acute pyelitis is not of common occurrence, but is usually 
found to exist as an accompaniment or a complication of an 
acute disease of the kidney proper. 

Causes. — The disease is usually produced in one of 
three ways : (i) By the extension of an inflammatory 
process downward from the kidney ; (2) by the upward 
extension of disease of the bladder ; (3) by irritants con- 
fined within the pelvic cavity itself An acute nephritis 
is usually accompanied by a more or less severe acute 
pyelitis (see p. 297) — in other words, the irritant that 
has set up the nephritis has also had its irritating influ- 
ence on the mucous membrane of the pelvis by extension 
downward. Not infrequently an acute pyelitis (together 
with an acute nephritis) follows exposure to cold and 
wet, and it may be set up by the irritating action of the 

333 



334 DISEASES OF THE URINARY TRACT. 

toxines of certain acute infectious diseases, such as typhoid 
fever, scarlet fever, diphtheria, and septicemia. A gonor- 
rheal infection of the lower urinary tract may, by exten- 
sion, result in an acute pyelitis, and sometimes, later, an 
acute nephritis. When an acute pyehtis occurs without 
an accompanying acute nephritis or disease of the lower 
urinary passages, it is almost invariably due to the irritat- 
ing action of crystalline elements or to a small concretion 
within the pelvic cavity. If due to a concretion, the inflam- 
matory process may be circumscribed. Rarely, the pressure 
of a new growth, which is located outside of the urinary 
tract, on the pelvis of the kidney results in an acute pyelitis. 

Prominent Symptoms. — There is usually more or less 
pain referred to the region of the affected kidney or kidneys, 
and it is often found radiating along the course of the ureter 
toward the groin. There is frequently some fever, although, 
as a rule, the temperature is not high. The disease may, 
however, be ushered in by a chill or a succession of rigors 
followed by a high temperature for a day or two. Hema- 
turia is an early symptom, and usually continues for several 
days. The patient may suffer from renal colic, caused by 
the marked irritation of crystalline elements or by a cal- 
culus or blood-clot obstructing the outflow of urine through 
the ureter. Rarely, a pyonephrosis results from obstruc- 
tion in the ureter. Micturition is more frequent than 
normal. The symptoms of an accompanying acute nephri- 
tis or a cystitis are often sufficiently prominent to entirely 
obscure those that are referable to the pelvis itself 

Character of the Urine. — The urine of a simple acute 
pyelitis, without much involvement of the kidney proper, 
usually has the characteristics of a fever urine. 

Quantity. — Considerably diminished — /. e., from 400 to 
800 or 1000 c.c. 

Color. — High, and frequently smoky, sometimes a blood- 
red color, depending upon the amount and character of the 
blood present. 

Specific Gravity. — -This is generally higher than normal 
^1025 to 1030, or as high as 1035. 

Normal Solids. — Absolutely, diminished ; relatively, in- 
creased. 

Albumin. — The quantity of albumin is variable, but in a 
general way corresponds to the amount of blood and pus 
present. As a rule, the quantity of albumin is chiefly rela- 



CHRONIC PYELITIS. 335 

tive to the amount of blood rather than to the quantity 
of pus present. The quantity usually varies between a 
slight trace and J^ of I per cent. 

Sediment. — Chiefly normal blood. Numerous small 
caudate cells from the superficial layer of the pelvis of the 
kidney. Some pus, both free and in clumps. There are, 
frequently, clumps of small, medium, or large round cells 
from the calices of the kidney. Since there is nearly always 
some extension of the inflammatory process into the straight 
tubules, a few (or occasional) granular and brown granular 
casts with adherent renal cells from the straight tubules, and 
abnormal blood will be found. If the tubular involvement 
is marked, the number of casts will be much larger, and the 
general characteristics of the urine will approach those of 
an acute nephritis complicated by an acute pyelitis. The 
presence of crystals or crystalline fragments should always 
be noted, for they may be the cause of the pyelitis, or may 
lead to the diagnosis of a calculus and the probable compo- 
sition of the same. 

An acute pyelitis as a complication of an acute nephritis 
or the result of an irritant toxine usually disappears with the 
subsidence of the primary affection. Sometimes it lasts 
only a few days and then, quite suddenly, the urine and 
sediment bear the characteristics of a chronic pyelitis. 
When the disease is due to the presence of a concretion or 
to a gonorrheal infection, it very soon becomes chronic, and 
may continue for months or years as a chronic pyelitis. 

CHRONIC PYELITIS. 

This is a chronic inflammation of the mucous membrane 
of the pelvis of the kidney. It may be mild or severe, and 
local or general. 

Causes. — A chronic pyelitis is induced by a variety of 
causes, among which the following are the most important : 
(i) The irritation by crystals or calculi — a very common 
cause. (2) Tuberculosis. (3) The infectious pyelitis that 
develops in fevers, in which an acute pyelitis precedes the 
chronic inflammation. (4) Obstruction to the outflow of 
urine through the ureter, as by an impacted calculus, blood- 
clot, stricture or twist of the ureter, etc. (5) The presence 
of decomposing urine, following pressure upon the ureter 
by tumors located outside the urinary tract. (6) A frequent 
cause of a chronic pyelitis is the upward extension of an 



336 DISEASES OF THE URINARY TRACT. 

inflammation of the bladder. (7) Obstruction to the out- 
flow of urine by a tight stricture of the urethra, a very nar- 
row prepuce, or tumor of the bladder. (8) Movable kidney. 

Prominent Symptoms. — In the forms of chronic pyelitis 
associated with the acute febrile diseases symptoms may 
be wanting. There may be more or less pain in the region 
of the affected organ. If, at any time, there is retention of 
the pus as the result of obstruction in the ureter or bladder, 
chills followed by fever, sweats, and sometimes renal colic 
ensue. Such symptoms rapidly disappear following an 
evacuation of the pus, but spontaneous evacuation of the 
pus cavity (renal pelvis) may not take place ; under these 
circumstances a true pyonephrosis results. Aside from 
twists of the ureter, perhaps the most common cause of 
frequent attacks of retention of pus, followed in a few days 
by evacuation of the pus cavity, is the presence of calculi 
in the renal pelvis, the obstruction being removed by a 
change of position or other means. A pyonephrosis with 
its attending symptoms is not an uncommon outcome of a 
chronic pyelitis. 

Character of the Urine. — The urine has the general 
characteristics of one of a chronic disease. 

Quantity. — Usually, less than normal — about 1200 c.c. 

Color. — Pale. The urine is generally very turbid, due to 
the pus in suspension. 

Reaction. — Usually, faintly acid. The urine readily be- 
comes alkaline upon standing. 

Specific Gravity. — This is below the normal — 10 10 to 
1015. 

Normal Solids. — Both absolutely and relatively, dimin- 
ished. The absolute quantity of urea will usually be found 
to vary between 15 and 25 grams ; the extent of the dimi- 
nution will depend upon the metabolism. 

Albumin. — This is relative chiefly to the amount of 
blood and pus present ; if the kidney proper is only slightly 
involved, the albumin will generally vary between a very 
slight trace and a large trace. 

Sediment. — Chiefly degenerated pus, both free and in 
clumps ; many small round cells, some in the clumps of 
pus ; a few blood globules. In most cases there is more 
or less involvement of the straight tubules of the kidney ; but 
renal casts are often difficult of detection in the sediment, 
owing to the presence of the pus which obscures them. 



CALCULOUS PYELITIS. 337 

In a chronic pyelitis the casts present, are usually of large 
diameter, and they may have leucocytes adherent to them, 
or there may be true pus casts. 

A careful search should always be made for crystals or 
cr>^stalline fragments, and when present the diagnosis of a 
calculous pyelitis is rendered probable. On the other hand, 
a concretion may exist in the renal pelvis without the pres- 
ence of any formed crystals, or crystalline elements, in the 
sediment. Great care should be taken not to mistake ex- 
traneous particles of dust, pieces of broken glass, etc., for 
fragments of a calculus. 

The urinary sediment should in all doubtful cases be 
examined for tubercle bacilli, for it is only by this means 
that a tubercular pyelitis can be eliminated. 

The diagnosis of a new growth involving the pelvis of 
the kidney is very difficult from the urine alone. Rarely, 
the presence of an unusual number of cellular elements 
leads to such a diagnosis, but such inferences should be 
well guarded by clinical signs and symptoms. 

Duration and Prognosis. — A chronic pyelitis usually 
disappears with the removal of the cause, if such is possible. 
If due to tuberculosis or a new growth of the kidney and 
its pelvis, surgical interference is usually necessary. 

There is constant danger of disease of the healthy kidney, 
and when it occurs, there is, unfortunately, little that can be 
done to relieve the condition. The disease in a mild form 
may continue for years without causing, in itself, much suf- 
fering. This is especially the case when the disease is caused 
by accidental twists of the ureter as in floating kidney, 
in v/hich instance the urine is retained in the renal pelvis 
until a time when the pressure of the retained fluid becomes 
sufficient to force its escape, or until the kidney regains its 
normal position by a sudden change of position of the 
patient, or until it is replaced by surgical operation. When 
the kidney is stitched into position, the chronic pyelitis 
usually subsides in a short time ; otherwise the disease may 
continue in a mild form as long as these temporary twists 
of the ureter occur. 

CALCULOUS PYELITIS. 

Although this subject has been considered in connection 
with an acute and chronic pyelitis, it deserves special atten- 
tion because of its importance. 



338 DISEASES OF THE URINARY TRACT. 

Calculi that cause pyelitis may be large or small, and 
ma}' be free in the pelvis or become encysted. They 
often have projections that extend up into the calices and 
sometimes into the straight tubules ; the tubules thus 
obstructed become dilated by the purulent urine, and 
often result in abscesses. When the pressure of the fluid 
in the abscess sac becomes sufficient to dislodge the 
obstructing calculus, the urine suddenly contains a large 
amount of pus, which is almost invariably of a greenish 
color. Sometimes there is a gradual leakage of pus about 
the seat of the obstruction, and not infrequently the abscess 
connects with one or more tubules, so that the urine con- 
stantly contains pus, and often in enormous quantities. The 
author has recently seen a case of multiple abscess of the 
kidney due to a large calculus in the pelvis, in which the 
pus sacs apparently had a common opening from which an 
enormous amount of pus was discharged — nearly one-fourth 
of the twenty-four-hour urine being thick greenish pus. 

In calculous pyelitis there may be only slight turbidit}^ of 
the mucous membrane, such a condition being sometimes 
called catarrhal pyelitis. ]\Iore commonly, the mucous sur- 
face is roughened, grayish in color, and thick. Under these 
circumstances there are almost always more or less dilata- 
tion of the calices and flattening of the papillae. Follow- 
ing this condition there may be (i) extension of the suppu- 
rative process to the kidney itself, forming a pyelonephritis. 
(2) A gradual dilatation of the calices with atrophy of the 
kidney substance, and, finally, the production of the condi- 
tion of pyonephrosis in which the entire organ is repre- 
sented by a sac of pus with or without a thin shell of renal 
tissue. (3) After the kidney structure has been destroyed 
by suppuration, if the obstruction at the orifice of the pelvis 
persists, the fluid portions may be absorbed, and the pus 
become inspissated, so that the organ is represented by a 
series of sacculi containing grayish pap-like masses, which 
have become impregnated with lime-salts. 

Prominent Symptoms. — The symptoms are, for the 
most part, the same as those in chronic pyelitis. There may 
be pain in the back or there may be tenderness on deep 
pressure on the affected side. Before the condition of 
pyuria is established, besides the attacks of pain, there may 
be rigors, high fever, and sweats. Pain is often increased 
bv exercise, — walkino; or ridincr, — but not in all cases. 



HYDRONEPHROSIS. 339 

Coincident with the retention of pus, a tumor may be felt 
on the affected side. The general condition of the patient 
usually indicates prolonged suppuration. Occasionally, 
nervous symptoms, which may be associated with dyspnea, 
supervene ; or the termination may be by coma. These 
nervous phenomena have been attributed to the absorption 
of the decomposed materials from the seat of the disease. 

Character of the Urine. — The urine generally has the 
characteristics of an acute or a chronic pyelitis. The most 
predominant element in the sediment is the pus, which is 
often present in large quantity. There is usually more or 
less blood, and sometimes it is present in considerable quan- 
tity. The sediment may, or may not, contain crystalline 
elements or concretions ; the mere absence of crystals 
would not be sufficient ground for excluding the condition 
of calculous pyelitis. 

Usually, the other (unaffected) kidney is more or less 
congested as a result of the elimination of toxines from the 
diseased organ. This is especially the case in chronic pye- 
litis or abscess of the kidney due to a stone, but it is often 
very difficult to find renal casts in the presence of so much 
pus. 

Diagnosis. — Between the tuberculous and calculous 
forms of pyelitis it may be difficult or impossible to distin- 
guish, except by the detection of tubercle bacilli in the 
urinary sediment. The examination for tubercle bacilli 
should be made systematically in all suspicious cases, and 
if not found by the microscope, guinea-pigs should be in- 
oculated with a portion of the sediment. 



HYDRONEPHROSIS. 

This is a condition due to an obstruction in the ureter and 
the retention of 7ionpiirulent urine in the pelvis of the kidney. 
If the obstruction continues, the pelvis of the kidney be- 
comes extremely dilated, and as a result of the back pres- 
sure there is a marked dilatation of the straight tubules, and 
then the smaller tubules. Finally, the kidney and its pelvis 
are converted into a sac, which may be of sufficient size to 
produce a tumor on the affected side. The kidney soon 
loses its function after the urine begins to back up into the 
small tubules, and, finally, the entire work of secretion and 
excretion is thrown on the other kidney. 



340 DISEASES OF THE URINARY TRACT. 

About from thirty-five to forty per cent, of these cases are 
congenital, the remainder may be acquired. The co7igenital 
causes comprise twists of the ureter upon its axis, undue 
obHquity of the ureteral opening into the bladder, redupli- 
cation, valve-like folds of the mucous membrane of the ure- 
ter, and imperforate ureter. The acquired causes are (i) an 
impaction of a calculus ; (2) a blood-clot in the ureter ; (3) 
stricture of the ureter, especially following traumatism ; (4) 
twist of the ureter, particularly in case of '' floating kidney," 
and if due to this cause, the condition usually continues until 
the pressure becomes sufficient to force an opening and 
allow the fluid to escape (intermittent hydronephrosis) ; (5) 
new growth in the pelvis or ureter, or one outside of the 
urinary tract, causing marked pressure on the ureter. 

Prominent Symptoms. — A dull, aching pain is usually 
present in the renal region. A tumor is present in most 
cases, gradually encroaching on the median line and down- 
ward toward the iliac fossa. A sudden diminution in the 
size of the tumor coincident with the elimination of an 
unusual quantity of nonpurulent urine, may be considered 
diagnostic. Vomiting sometimes occurs during these periods 
of retention, and occasionally a urinous odor may be observed 
in the perspiration at such times, especially if both kidneys 
are involved. Constipation is a frequent result of pressure 
upon the colon ; more rarely, diarrhea may be present from 
the same cause. As long as the hydronephrosis is single 
and the remaining kidney healthy, there is usually an 
absence of uremic symptoms. Enlargement of the unaf- 
fected kidney may compensate for the defective elimination. 
Hypertrophy of the left side of the heart usually follows. 

Character of the Urine. — Owing to the virtual loss of 
function of the affected kidney, the entire work of elimina- 
tion is thrown on the other kidney and, as a result, it is 
common to find evidence of more or less active congestion 
of the unaffected organ. (See Active Hyperemia.) The 
quantity of urine is generally diminished ; the normal solids 
are absolutely diminished, although not to a marked degree ; 
and there is usually albumin, varying between the slightest 
possible trace and a trace. The sediment usually contains 
an occasional (or few) hyaline, granular, and brown granu- 
lar casts, some of which have renal cells and a little abnor- 
mal blood adherent ; and a few free renal cells and blood 
globules. 



PYONEPHROSIS. 341 

In rare instances the urine may be perfectly normal. 

The fluid in the Jiydroncphrotic sac is usually of a pale 
color, of low specific gravity, and contains only small 
amounts of the normal urinary constituents, notably urea 
and uric acid. Albumin is generally present, the quantity 
being in the neighborhood of a trace. The .$-^<^/;;/^;// usually 
consists of a few blood globules, cells from the pelvis and 
tubules of the kidney, and a few casts of small diameter 
from the higher tubules. There is no pus, or, at the most, 
only an occasional leucocyte. 

The outlook in hydronephrosis depends upon the cause. 
When unilateral, the condition may never produce serious 
trouble, and the intermittent forms may persist for years and 
finally disappear. Occasionally, the cyst ruptures into the 
peritoneum, more rarely through the diaphragm into the 
pleural cavity and lung. The sac may discharge spontane- 
ously through the ureter and the fluid never reaccumulate, 
or the condition may change to one of pyonephrosis. 



PYONEPHROSIS. 

This condition is the result of an obstruction to the out- 
flow of urine through the ureter, and the retention of puru- 
lent urine in the renal pelvis. It usually follows a pre- 
existing acute or chronic pyelitis, although it may exist 
primarily as a hydronephrosis, and later become a pyo- 
nephrosis as a result of the inflammatory process set up by 
chemic or mechanical irritants in the pelvis — notably ciys- 
talline elements or a calculus. 

The destruction of the kidney is sometimes very rapid, 
because of the retained pus-containing fluid and the ex- 
tension of the inflammatory process to various parts of the 
kidney proper. As in hydronephrosis, the back pressure 
of the retained fluid results, first, in a marked dilatation of 
the renal pelvis ; next, the straight tubules ; then, the smaller 
tubes, which become atrophied and lose their function ; and, 
finally, the disorganized kidney and its pelvis constitute a 
large pus sac. 

Causes. — Any of the causes ascribed to a hydronephrosis 
may produce a pyonephrosis by partially or entirely oc- 
cluding the ureter, if a pyogenic organism be present. 
Of these the most common are impacted calculus, twist 
of the ureter in case of ''floating kidney," and trau- 



342 DISEASES OF THE URINARY TRACT. 

matic or inflammatory stricture of the ureter. Marked pres- 
sure on the ureter or the pelvis of the kidney by new growths 
that are situated outside of the urinary tract may produce 
this condition. 

Prominent Symptoms. — The most prominent symptoms 
of pyonephrosis comprise pyuria with constitutional symp- 
toms, such as chills, irregular temperature, emaciation, 
anemia, and prostration. If there is a tumor, it may be 
elastic and fluctuating, or hard, and extend both forward 
and downward. Pain is present, varying with the size of 
the tumor and degree of fluctuation ; it often appears in 
paroxysms of intensity — rejial colic. Pressure over the 
anterior of the tumor greatly increases the pain, or causes 
it if not present before. On the other hand, lateral pressure 
may relieve the pain when present. The bowels are usually 
disturbed, constipation or diarrhea being frequent. The 
sudden appearance of a purulent urine that has previously 
been clear and free from pus is often of great diagnostic 
value. 

Character of the Urine. — If the pyonephrosis is uni- 
lateral and the occlusion of the ureter on the affected side is 
complete, the urine usually shows the existence of a more or 
less severe active hyperemia of the unaffected kidney. This 
is undoubtedly due partly to the absorption of toxic prod- 
ucts from the diseased kidney, and partly to the extra work 
of elimination. The urine will be free from pus and other 
evidences of a pyonephrosis, so that the diagnosis of this 
condition can only be made from the physical examination 
and the clinical symptoms. 

If by any means the obstruction in the ureter be re- 
moved, the urine will suddenly become very turbid, and 
when it settles will contain a very abundant sediment hav- 
ing a decidedly greenish tint. On microscopic examination 
this sediment will be found to consist of a large quantity 
of degenerated and disintegrated pus, accompanied by an 
abundance of small round cells. There may be a small 
amount of blood in this sediment, but usually blood- 
corpuscles are difficult to find — or, more properly, difficult 
to recognize — in the presence of so much pus. 

The odor of the urine containing the pus is generally 
very offensive, and sometimes the reaction is alkaline. 

The quantity of albumin is usually large, — yi to j^ of i 
per cent, or more, — and very often the albumin is accom- 



URETERITIS. 343 

panied by an abundance of globulin. The author has met 
with one case in which the quantity of globulin equaled 
that of the albumin. From a diagnostic point of view the 
other characteristics of the urine are not especially significant. 

It is often necessary to remove the diseased kidney in 
order to save the life of the patient. The pus sac thus 
removed usually contains very little, if any, fluid material, 
but, instead, a thick, putty-like or cheesy mass of inspis- 
sated pus, the liquid portion having been previously ab- 
sorbed. This putty-like substance may contain a deposit 
of lime-salts. 

A pyonephrosis is always attended with danger to life. 
Perforation into the peritoneal or pleural cavities may 
occur, or the patient may be worn out by the hectic fever, 
or amyloid disease may develop. 



URETERITIS. 

An inflammation of the mucous membrane of the ureter 
may be acute or chronic. The inflammatory process may 
be local or general, according to the cause. 

A diagnosis of this condition from the urine alone is 
practically impossible, especially if the urine is voided in 
the natural way. Since the advent of catheterization of the 
female ureters, exceptional opportunities have been afforded 
for studying diseases of this tract, and some instructive 
observations have been made. 

Causes. — This inflammatory condition may be a part of 
an acute pyelitis or an acute cystitis, by extension. It is 
probably more frequent in connection with an acute pye- 
litis, and often due to the same causes. (See p. 333.) 
Aside from an inflammatory process due to exposure to 
cold and wet, perhaps the most common cause is the pas- 
sage of calculi or microscopic crystals of uric acid or cal- 
cium oxalate. If the calculus can not be forced through 
the ureter, it first produces a marked acute ureteritis and 
later a chronic inflammation at its lodging point, which is 
frequently at the place where the ureter crosses the brim of 
the pelvis. The microscopic crystals often produce an irri- 
tation or inflammation of the mucous membrane through- 
out the entire length of the tube. Like an acute pyelitis, 
the acute process in the ureter soon becomes chronic. The 
inflammation may have the characteristics of a chronic 



344 DISEASES OF THE URINARY TRACT. 

ureteritis from the beginning, as in tubercular ulcerations, 
or a gradual extension upward of a chronic inflammation 
of the bladder. The pressure on the ureter by new growths 
located outside of the urinaiy tract, twists, and strictures of 
the ureter often produce more or less inflammation. 

Symptoms. — The most prominent clinical feature is the 
paroxysmal sharp pain — renal colic — that starts in the 
region of the kidney, follows down the line of the ureter 
into the testicle, and along the inner side of the thigh. 
During the paroxysm of pain there is usually nausea and 
vomiting, marked prostration, and sometimes a little fever. 
(See Renal Calculus.) On bimanual examination the 
thickened ureter or impacted calculus can, occasionally, 
be felt through the abdominal wall. 

Character of the Urine. — The urine usually has the 
characteristics of the inflammatory process above or below 
the ureter — acute or chronic pyelitis, and acute or chronic 
cystitis. The diagnosis of a simple ureteritis, if such exists 
without a pyehtis or cystitis, can only rarely be made from the 
urine alone ; even then it is very difficult to distinguish it from 
an irritation or acute inflammation of the pelvis of the kid- 
ney. In a simple ureteritis due to an impacted calculus the 
urine usually has a high color, strongly acid reaction, and 
high specific gravity. The quantity of albumin commonly 
varies with the amount of blood. The sediment frequently 
contains more or less blood, and sometimes the blood is 
present in abundance. There are usually small caudate 
and spindle cells from the ureter, and a few (or numerous) 
leucocytes. 

Catheterization of the ureters may lead to the diagnosis 
of ureteritis, stricture of the ureter, or the presence of a cal- 
culus in the ureter. The history of renal colic, or of more 
or less continuous pain in the region of the ureter, is of 
importance in the diagnosis. 



CYSTITIS. 

This is an inflammation of the mucous membrane of the 
bladder ; it may be either acute or chronic. 

ACUTE CYSTITIS. 

Causes. — One of the most common causes of this disease 
is an infection with micro-organisms, such as the gonococ- 



ACUTE CYSTITIS. 345 

cus in cases of backward extension of a gonorrheal ure- 
thritis ; with the pyogenic staphylococci and other forms of 
pyogenic bacteria that have been introduced into the bladder 
by means of an unclean catheter ; and with the tubercle 
bacillus. It may result from an acute prostatitis ; from in- 
jury, as with the rough use of sounds ; from extensive ure- 
thral stricture ; from foreign bodies, such as calculi ; from 
drugs, such as cantharides and copaiba ; and from new 
growths. An acute cystitis is not uncommonly seen fol- 
lowing exposure to cold and wet, sexual excesses, and 
simple acute retention of urine. An acute inflammation 
of the bladder is a frequent complication of acute infec- 
tious diseases, notably typhoid fever, in which case it is 
probably the direct result of the action of the typhoid 
bacillus. 

In the mild cases of acute cystitis the vesical mucous 
membrane is congested, thickened, and swollen, and the 
epithelium becomes detached in places, leaving abraded sur- 
faces. In the severe forms the bladder becomes lined with 
a tough, tenacious layer of mucin (?) ; there may be ulcera- 
tions and sloughing. The submucous connective tissue is, 
in some cases, infiltrated with pus, and hemorrhagic areas 
are not uncommon. 

Prominent Symptoms. — One of the first symptoms is 
increased frequency of micturition, which usually becomes 
more and more prominent, only a very small quantity of 
urine being voided at each effort at urination. Tenesmus is 
frequently very severe ; the patient will often lean over the 
vessel or urinal, quivering with the muscular effort, without 
relief to the distressing and very urgent desire. The pain, 
which is likewise extreme, may be referred to the neck of 
the bladder, to the perineum, to the glans penis, or to the 
hypogastrium, and may radiate into the loins or down the 
thighs. There is frequently marked constitutional disturb- 
ance with more or less elevation of temperature, although in 
some cases the general disturbance is slight in comparison 
with the intensity of the local symptoms. 

Character of the Urine. — Quantity. — The twenty-four- 
hour quantity of urine is usually small, varying from 500 to 
800 or 1000 c.c. 

Color. — Bloody or smoky, depending upon the amount 
and character of the blood present. 

Reaction. — Strongly acid. 



346 DISEASES OF THE URINARY TRACT. 

Specific Gravity. — Early in the disease the specific 
gravity is usually high — 1025 to 1030; later, it is normal 
or slightly diminished — 1015 to 1022. 

Normal Solids. — Relatively, increased ; but absolutely, 
more or less diminished, depending upon the amount of 
systemic disturbance set up by the disease. 

Albumin. — The quantity of albumin is variable, but in 
a general way it is relative to the amount of blood and pus 
in the urine. It is not uncommon for the quantity of albu- 
min to reach or even exceed y^ of i per cent., but usually 
it is less than this figure. 

Sediment. — The sediment, which is generally abundant, 
consists chiefly of normal blood ; considerable pus, some in 
clumps, and a large amount of squamous epithelium. 
Numerous small round cells, perhaps some of them fatty, 
may be found. 

CHRONIC CYSTITIS. 

Causes. — A chronic cystitis may result from an acute 
cystitis. In some instances the changes taking place in the 
mucous membrane of the bladder are so slight and gradual 
that a chronic process results apparently without a preexist- 
ing acute stage. In general, the same causes that have 
been attributed to an acute inflammation of the bladder may 
be looked for to explain the presence of a chronic cystitis. 
Among these causes are to be borne in mind infection 
by micro-organisms, as following the introduction of insuf- 
ficiently purified and disinfected catheters or bougies, or 
when the instrument carries into the bladder pus and bacte- 
ria from an ulcerating surface or a pus pocket in the urethra 
(stricture). A very frequent cause of this form of cystitis 
is the enlarged prostate. Owing to the inability of the 
patient to completely empty his bladder, the residual urine 
sooner or later decomposes by the rapid development of 
bacteria, and a general cystitis results. In a similar manner 
many cases of cystitis arise in patients with nervous disease, 
who have paralysis of the bladder, as in paraplegia ; also 
in persons who are severely ill and stupid from some acute 
disease, such as typhoid fever. In the acute infectious dis- 
eases a chronic cystitis may appear, either as the result of 
frequent catheterization, or by the action of the bacteria 
causing the disease. 

In cases of vesical calculus, vesical tuberculosis, and new 



CHRONIC CYSTITIS. 347 

growths of the bladder, a chronic cystitis is probably more 
commonly seen than an acute cystitis, since the disturbance 
by these agencies is at first slight. The subsequent changes, 
which are often very gradual, become more pronounced, 
and finally a well-marked chronic inflammatory process is 
apparent. 

In women the agents of inflammation may quite easily 
enter the bladder from the vagina through the short female 
urethra ; thus arise the frequent cases of cystitis in childbed 
(usually an acute cystitis). Communications may develop 
between the bladder and certain neighboring organs, such 
as vesicorectal or vesicovaginal fistulae, by which, again, 
access to the bladder is open to the agents of inflammation. 

The pathologic changes in the wall of the bladder may 
result in atony or atrophy, with thinning of the mucous 
membrane, fatty degeneration of the muscular fibers almost 
to the point of disappearance, and great distention of the 
organ. Again, they may be followed by hypertrophy of 
the muscular coat, the fibers forming ridges or fasciculi 
standing out in the interior of the bladder and separated by 
lozenge-shaped spaces, the organ itself being contracted so 
that its cavity can contain but a few cubic centimeters of 
fluid. Sometimes between these muscular bars pouches of 
mucous membrane protrude, forming distinct sacculi com- 
municating with the interior of the bladder by narrow 
mouths and remaining permanently ; occasionally, they 
contain calculi. In chronic cystitis of long standing the 
mucous membrane often takes on a slaty, grayish-black 
color as a result of hemorrhages. The incrustation of the 
mucous membrane with urinary salts, especially with am- 
monio-magnesium phosphate, is also frequently found in the 
chronic form of this disease. 

Prominent Symptoms. — The symptoms of an acute 
cystitis are present in a modified form. Micturition is not 
so frequent ; tenesmus is much less or is absent (in mild 
cases) ; pain is usually very slight, and in mild cases it may 
be absent ; the constitutional symptoms are comparatively 
slight, and become marked only when renal changes have 
occurred or when a general toxemia has followed the 
absorption of the products of urinary decomposition. 

Character of the Urine. — Quantity. — The twenty-four- 
hour quantity of urine is usually only moderately diminished 
— /. c, 800 to 1400 c.c. 

Color. — Generally pale, but it may be normal in color ; 



348 DISEASES OF THE URINARY TRACT. 

it may, however, be tinted with blood to a greater or less 
extent. The freshly passed urine is generally turbid, due to 
the presence of pus and epithelium and an abundance of 
bacteria. 

Reaction. — Frequently alkaline, but it may be acid and 
sometimes it is strongly acid, especially in the early stages 
of the disease. The reaction varies according to the pres- 
ence or absence of urea-decomposing organisms. 

Specific Gravity. — This varies usually between 1012 
and 1020; average about 1015. 

Normal Solids. — Both relatively and absolutely^ dimin- 
ished. 

Albumin. — This varies between the slightest possible trace 
(mild cases) and ^ of i per cent, (severer forms). It is 
usually directly dependent upon the amount of pus and 
blood present. 

Sediment. — Abundant. If the urine be acid, the sedi- 
ment will consist chiefly of pus and small round cells ; con- 
siderable squamous epithelium, and generally a small 
(sometimes a considerable) amount of blood. If the urine 
be alkalijte, — ammoniacal, — the sediment will settle in a 
viscid, sticky mass, which consists mostly of decomposed 
pus, amorphous phosphates, crystals of triple phosphate, 
and often crystals of ammonium urate. The pus corpuscles 
may be so embedded in the mucin-like substance and so 
changed as to entirely lose their characteristic appearance. 

There can be no doubt that decomposing alkaline urine 
acts as a chemic irritant to the mucous membrane of the 
bladder ; hence, cases of mild cystitis often become inten- 
sified by the irritation of the ammonia salts that are formed. 

The longer a chronic cystitis continues, the greater the 
likelihood of the development of a pyelonephritis. In this 
way a cystitis, especially in chronic diseases of the nervous 
system and in old age, may become the immediate cause of 
death. 

TUBERCULOSIS OF THE BLADDER, 

Tuberculosis of the bladder is not an uncommon condi- 
tion. The existence of a chronic inflammation of the blad- 
der, in the absence of tangible evidences of infection from 
gonorrhea, chronic obstruction, or by instrumentation, 
should always leave a suspicion of the tubercular nature of 
the affection. The two places in which tuberculosis of the 
bladder is most likely to commence are the trigone and 



TUBERCULOSIS OF THE BLADDER. 349 

ureteral orifices, the latter being the more common. The 
tubercular process begins with the formation of typical gray 
nodules in the mucous membrane ; these nodules become 
confluent, caseate, soften, and finally produce ulceration. 
In more acute cases the disease leads to diffuse cheesy infil- 
tration and general ulceration. 

Vesical tuberculosis is found more frequently in males 
than in females, and is a disease of early and middle life 
(seventeen and forty years of age). In the male the disease 
is frequently associated with tuberculosis of the seminal vesi- 
cles and of the prostate. The resistance of the mucous 
membrane of the bladder to tubercle bacilli is quite marked ; 
in some cases of tuberculosis of the kidney the bladder may 
be irrigated with urine containing tubercle bacilli for years 
without becoming tubercular. 

Prominent Symptoms. — The symptoms of vesical tuber- 
culosis are similar to those of stone in the bladder. The 
disease is initiated by a frequent desire to urinate, by pain 
after emptying the bladder, with slight hematuria at longer 
or shorter intervals. Later in the disease intermittent 
hemorrhage becomes a conspicuous clinical symptom, but 
it is never so profuse as in tumor of the bladder. Reten- 
tion and incontinence of urine are quite common. 

Character of the Urine. — Quantity. — The twenty-four- 
hour quantity is usually diminished, although it may be 
slightly increased. 

Color. — Pale ; sometimes bloody. The urine is gener- 
ally quite turbid from the pus, blood, etc., in suspension. 

Reaction. — Nearly always acid, except when the urine 
contains a large amount of blood, when it may be neutral 
or alkaline. 

Specific Gravity. — Usually, below the normal — loioto 
1015. 

Normal Solids. — Relatively and absolutely ^ diminished. 

Albumin. — The quantity will depend chiefly on the 
amount of blood and pus present ; it usually varies between 
a slight trace and a large trace. In case of abundant hema- 
turia the quantity of albumin will, of course, be high — ^ 
to i^ of I per cent. 

Sediment. — Abundant. Chiefly pus, which is generally 
free, but may be slightly clumped. Considerable squamous 
epithelium and many small round cells, some of which are 
fatty ; a few (sometimes numerous) blood globules. The 
sediment also contains tubercle bacilli. 



350 DISEASES OF THE URINARY TRACT. 

As in tuberculosis of other parts of the urinary tract, 
the symptoms are variable and often misleading. Even the 
presence of tubercle bacilli in the urine, indicating as it 
does tuberculosis of the urinary system, does not locate the 
anatomic seat of the disease. The presence of tubercle 
bacilli and squamous epithelium, which are more or less inti- 
mately mixed with the pus, makes the diagnosis of vesical 
tuberculosis probable. 

The prognosis in this condition is usually grave. Spon- 
taneous recovery is exceedingly rare. If the disease be 
mild and limited to the bladder, it may remain in a latent 
condition for years. There is always danger of an exten- 
sion of the tubercular process to the kidney, which is soon 
followed by a suppurative pyelonephritis. There can be 
but little doubt that appropriate general and local treat- 
ment will prolong life and alleviate the distressing symp- 
toms. 

In all cases of cystitis in which the cause of the disease 
is not obvious the urinary sediment should be very care- 
fully searched for tubercle bacilli. In case the organisms 
can not be found a guinea-pig should be inoculated with a 
portion of the sediment (^ to i c.c), and the result of this 
experiment obtained, before eliminating the diagnosis of 
tuberculosis. (See Detection of Tubercle Bacilli in the 
Urinary Sediment, p. 325.) 

TUMORS OF THE BLADDER. 

Tumors of the bladder may be either benign or malig- 
nant. 

The benign tumors include the fibromata, fibromyx- 
omata, and papillomata ; of these the latter are by far the 
most frequent. Fibromata and fibromyxoinaJa grow from 
the submucous coat of the bladder ; they are either sessile 
or pedunculated, and are covered by unaltered mucous 
membrane or by villi. Papillomata grow from the super- 
ficial layer of the mucous membrane ; they appear as red 
vascular masses, usually with long pedicles, and occasion- 
ally they are sessile. Sometimes the papillae are long and 
slender and float in the urine in numerous filaments from a 
common base ; sometimes the mass has a cauliflower ap- 
pearance, this form of tumor constitutes the so-called villoits 
grozuth of the bladder. (In Fig. 53 the masses represent 
small portions of very small villi in which characteristic 



TUMORS OF THE BLADDER. 351 

small caudate cells are arranged about a central cone of 
fibrous tissue, blood-vessels, etc. The caudate cells have 
prominent and relatively large nuclei, and are somewhat 
larger than the average cell from the superficial layer of the 
pelvis of the kidney. In papillomatous disease of the 
bladder cells of this kind may be found in the sediment 
singly or in clumps.) Frequently, they undergo ulceration ; 






; *- X? I' 



CI 






b 



Fig- 53-— Portions of a villous growth of the bladder : a, Magnified 190 diameters ; 
b^ magnified 370 diameters. 

they sometimes bleed very freely. Nearly all vesical 
growths tend to assume a papillomatous character. When 
the fibrous elements are numerous, the structure is denser ; 
this constitutes the fibropapilloma. There is reason to be- 
lieve that a growth originally purely papillomatous may 
become malignant in its later stages (" American Text- 
book of Surgery "). 



352 DISEASES OF THE URINARY TRACT. 

Malignant tumors of the bladder, although for the most 
part papillomatous, belong either to the order of sarcomata 
or to carcinomata. (See Cancer of the Prostate.) 

The prominent symptoms of tumor of the bladder are 
those of a chronic cystitis. (See p. 347.) Intermittent 
hematuria is a common symptom. Pain is usually not so 
marked as in the average case of chronic cystitis, and it 
may even be absent, especially if the disease does not in- 
vade the trigone (Fenwick). Frequency of micturition is 
an early and constant symptom. 

Character of the Urine. — The urine has much the same 
characteristics as in chronic cystitis, except that the reaction 
is generally acid ; there is a bloody or smoky color, and on 
account of the quantity of blood, a comparatively high 
percentage of albumin. Blood may be present in large 
amount; in fact, the quantity of blood is often greater than 
in almost any other disease of the urinary tract. Large 
blood-clots may partially fill the bladder, and not infre- 
quently they are the cause of retention of urine. The 
blood is usually not so intimately mixed with the urine as 
when it comes from the kidney. 

After the urine has settled and the blood has been de- 
stroyed (see p. 233), shreds are frequently seen floating in 
the urine. Upon microscopic examination these may be 
found to consist of pus and cells embedded in mucin, or 
bits of tissue perhaps resembling the mass represented in 
figure 53 (villous growth). Inferences as to the nature 
of these shreds — whether malignant or benign — can not 
usually be drawn from a microscopic examination of the 
sediment. Sometimes, as previously stated, the sediment 
contains caudate cells, single or in clumps, which will lead 
to the diagnosis of villous growths. Likewise, medium and 
small round and irregular cells with prominent and rela- 
tively large nuclei may be found, suggesting a new growth 
of the bladder. Usually, the epithelial elements are a pre- 
dominant feature of the sediment. 

Following the introduction of sounds or bougies into the 
bladder, the urine often contains cells ("caudate, large and 
small round) that have been mechanically detached from 
the mucous surface. These cells are found both singly and 
in clumps ; and care should be taken not to mistake them 
for cells of a new growth. 



ACUTE PROSTATITIS. 353 

PROSTATITIS, 

An inflammation of the prostate gland may be either 
acute or chronic, and parenchymatous or folUcular. 

In the parenchyviatotis form the inflammation afiects the 
whole substance of the gland, and constitutes the severer 
acute forms of prostatitis. 

ACUTE PROSTATITIS (PARENCHYMATOUS)* 

Causes. — Among the causes of this condition may be 
enumerated gonorrhea, urethral stricture, extreme and pro- 
longed sexual excitement, concentrated and highly acid 
urine, exposure to cold and wet, violence from instruments, 
fragments of calculi, trauma, etc. It may also result from 
the action of chemic irritants, strong urethral injections, the 
internal administration of cantharides, etc. Gonorrheal in- 
flammation, after the first week, may extend to the prostate, 
particularly if the patient indulges in liquor, sexual inter- 
course, or uses strong injections throwing them deep into 
the urethral canal, or takes violent exercise. Sometimes, 
during gonorrhea, the prostate becomes inflamed without 
an exciting cause. The inflammation behind a stricture 
may extend back and involve the prostate in the same way. 
Sexual hyperemia, too much prolonged or too often re- 
peated, may lead to an acute prostatitis. 

Prominent Symptoms. — The organ swells rapidly, put- 
ting the capsule on the stretch, and often reaches the size of a 
small orange. The exploring finger in the rectum strikes at 
once against an unevenly enlarged mass that projects into 
the cavity of the intestine. It is very tense and hot, ex- 
tremely tender, and can be felt distinctly to pulsate. The 
lightest touch, even the presence alone of the finger in the 
rectum, at once excites a marked desire to micturate ; pres- 
sure over the pubes has the same result. The patient may 
have an unnatural desire to defecate ; if he endeavors to 
do this, he strains ineffectively, causing pain, but getting no 
relief. There is subjectively a feeling of weight, heat, and 
throbbing, and sometimes pain in the back and limbs. The 
stream of urine is usually small, and occasionally there is 
complete retention of urine as a result of the swelling. 
Almost invariably there are an associated congestion of the 
vesical neck and a consequent extreme tenesmus. The urine 
causes pain in its passage, but the pain is most severe when 
23 



354 DISEASES OF THE URINARY TRACT. 

the last drops of urine are being expelled. There is gener- 
ally febrile disturbance, and the patient is usually irritable, 
despondent, and suspicious. 

Character of the Urine. — Quantity. — The twenty-four- 
hour quantity is small — generally between 500 and 1000 c.c. 

Color. — High or bloody. 

Reaction. — Strongly acid. 

Specific Gravity. — Usually high — 1025 to 1035. 

Normal Solids. — Relatively, increased; absolutely^ 
diminished. If the acute process lasts more than two or 
three days, the solids will be much diminished absolutely. 

Albumin. — Usually between ^ and ^ of i per cent. ; 
but the quantity is dependent chiefly on the amount of 
blood and pus present. 

Sediment. — Chiefly normal blood. Considerable pus, 
both free and in clumps ; many small round cells and a 
marked excess of cells from the prostatic region (neck of 
bladder) ; frequently there are spermatozoa and cells from 
the seminal passages. Occasionally, casts of the prostatic 
ducts are present, and with difficulty distinguished from 
casts of the renal tubules, which may also be present as a 
result of a coincident renal congestion. 

Diagnosis. — The clinical picture of the case is generally 
sufficient for a diagnosis without an analysis of the urine. 
In some instances, however, the diagnosis between an acute 
prostatitis and acute cystitis is not easy, but can often be 
made by attention to the following points : 

Acute Prostatitis. Acute Cystitis. 

Perineal and rectal pain. Possibly a little tenderness of the 

perineum on pressure, but little or 
no rectal pain. 
Pain violent and throbbing, aggra- Pain burning, not especially affected 

vated during defecation. by defecation. 

Stream of urine diminished in size. Size of stream not usually affected. 

Retention of urine common. Retention of urine much less com- 

mon. 
Rectal examination shows enlarge- No prostatic enlargement or tender- 
ment and extreme tenderness of the ness recognizable on rectal exam- 

prostate, ination. 

Urinary sediment contains blood, pus. Urinary sediment contains, besides 
marked excess of epithelium from blood and pus, much squamous 

prostatic region, spermatozoa, and epithelium, usually no marked ex- 

prostatic casts. cess of cells from prostatic region, 

and no spermatozoa nor prostatic 
casts. 

A greater or less involvement of the neck of the bladder 
is often an accompaniment of an acute prostatitis. 



PROSTATIC ABSCESS. 355 

PROSTATIC ABSCESS. 

An abscess of the prostate is liable to form as the result 
of a parenchymatous inflammation of the organ. There may 
be one or more purulent foci, or the whole substance of the 
prostate contained within its fibrous capsule may suppurate. 

The symptoms are in many respects similar to those of 
an acute prostatitis. A sharp chill or a series of rigors 
announces the beginning of suppuration. As the pus 
forms it presses upon the already narrowed canal of the 
urethra ; and, finally, unless the abscess is very small, 
obliterates it entirely, causing retention of urine. There 
are usually local throbbing and lancinating pain. These 
abscesses, left alone, discharge into the bladder, urethra, 
rectum, or through the perineum. When such an abscess 
opens spontaneously, all pain and discomfort are immedi- 
ately relieved. A small purulent collection in the prostate 
may empty itself gradually into the urethra by one or 
more minute openings ; in such cases the diagnosis of a 
prostatic abscess is not easily made. 

Character of the Urine. — This will vary according to 
circumstances : If the abscess is forming and has not yet 
opened, the urine will be concentrated, of high color, and 
high specific gravity, containing a very small amount of 
albumin ; the sediment will consist of a few leucocytes, 
blood globules, and an excess of cells from the neck of the 
bladder or prostatic urethra — in other words, -di fever urine, 
in which the sediment presents the evidences of an irrita- 
tion in the prostatic region. On the other hand, if the 
abscess has ruptured, the urine, with the exception of 
the sediment, will present the characteristics of that of 
severe chronic prostatitis. The sediment, which is abundant 
and often greenish in color, will consist chiefly of pus, both 
free and in clumps, that in clumps usually being much 
degenerated ; many small round cells, some fatty, and 
generally a few compound granule cells ; and few or num- 
erous blood globules. There is also an excess of cells 
from the prostatic region. 

CHRONIC PROSTATITIS. 

Causes. — A chronic inflammation of the prostate gland 
may be the result of an acute prostatitis. In some in- 
stances, as following sexual excesses, masturbation, etc., the 



356 DISEASES OF THE URINARY TRACT. 

pathologic process in the organ starts as a shght irritation 
that gradually increases, finally becoming a well-marked 
chronic condition without passing through an acute stage. 
A chronic prostatitis may result from stricture of the urethra, 
contracted meatus, phimosis, hypertrophy of the prostate in 
persons past the age of fifty-five, tuberculosis, trauma, irri- 
tation by crystalline elements, etc. 

Prominent Symptoms. — Perhaps the most prominent 
symptom of this condition is frequency of micturition. 
There are usually some pain and a feeling of uneasiness at 
the neck of the bladder, especially toward the close of uri- 
nation, and often pain at the end of the penis and along 
the under surface of the urethra. There may be a muco- 
purulent discharge from the urethra, but this is not gen- 
erally the case. Defecation is sometimes painful. Walk- 
ing causes pain, and crossing the legs decidedly increases 
it. As the disease advances, the sitting posture be- 
comes painful. Retention of urine is common. Constitu- 
tional disturbance may be absent, particularly in mild 
cases ; when the disease is marked, however, there may be 
more or less fever and mental depression. The finger in 
the rectum may find slight enlargement and at times detect 
extra sensibility. 

If the disease is the result of JiypertropJiied prostate^ not 
only will the enlargement be apparent to the finger in the 
rectum, but signs of mechanical obstruction to the outflow 
of urine will be prominent ; the stream will be interrupted 
and show a lack of force ; the patient will be unable to 
completely empty the bladder, only passing that which is 
in excess. This ''residual" urine may remain stationary 
in amount, but more often it gradually increases until, in 
some cases in which both hypertrophy of the prostate and 
atony of the bladder are marked, only an ounce or two of 
urine can be evacuated voluntarily, although catheterization 
will show that the bladder contains possibly a pint or more. 
The decomposition of the retained urine invariably results 
in a chronic cystitis ; often a pyelonephritis develops ; 
general sepsis occurs ; and the patient becoming uremic 
dies during coma. 

Fortunately, a fatal termination is not the outcome of all 
cases of chronic prostatitis ; some are amenable to treatment 
and entirely recover, especially the milder cases and those 



CHRONIC PROSTATITIS. 357 

which are not tubercular, or those in which an abscess of the 
prostate has not developed. 

Character of the Urine. — Quantity. — The total quantity 
for twenty-four hours is usually between 800 c.c. and 
1200 c.c. 

Color. — Pale. The urine is generally turbid, due to the 
presence of a large amount of pus in suspension. 

Reaction. — Usually acid ; if there is an accompanying 
chronic cystitis, the reaction may be alkaline, especially in 
cases of hypertrophy of the prostate. 

Specific Gravity. — This will generally be found to vary 
between 1012 and 1018 — average about 10 15. 

Normal Solids. — Both relatively and absolutely, dimin- 
ished ; the degree of diminution will depend largely on the 
amount of constitutional disturbance. 

Albumin. — The quantity of albumin will depend on the 
amount of pus and blood ; it usually varies between a very 
slight trace and yi of i per cent. In case there is an accom- 
panying disturbance or disease of the kidney the amount of 
albumin will be proportionately higher. 

Sediment. — This is abundant, and consists chiefly of pus, 
both free and in clumps ; many small round cells, some of 
which are fatty ; also an excess of cells from the neck of the 
bladder and prostatic urethra ; a few (sometimes numerous) 
blood globules ; and sometimes spermatozoa, and the highly 
granular cells from the seminal passages. Prostatic plugs 
(cylinders of long diameter resembling large renal casts or 
bodies of irregular shapes from dilated ducts or cavities), 
sometimes with spermatozoa embedded, are of frequent 
occurrence, especially in the mild (follicular) forms of 
chronic prostatitis. Frequently, the sediment contains large 
and small shreds that will be found to consist of pus, small 
round cells, and dense cells from the prostatic region, which 
are embedded in mucin (nucleo-albumin). If there is an 
accompanying chronic cystitis, as is the rule in cases of 
hypertrophied prostate, the sediment will contain more or 
less squamous epithelium, and frequently crystals of triple 
phosphate. A renal disturbance that is probably indirectly 
due to the chronic prostatitis, and perhaps the result of the 
absorption of toxines, is not uncommon. An occasional or 
a few renal casts may be found in the sediment, which are 
sometimes distinguished with difficulty on account of the 
abundance of pus. 



358 DISEASES OF THE URINARY TRACT. 



TUBERCULAR PROSTATITIS. 

This disease of the prostate is almost invariably associ- 
ated with tuberculosis of some other part of the genito- 
urinary tract. The disease occurs in tubercular, debilitated 
subjects, its chief feature being cheesy degeneration, situ- 
ated for the most part in the ducts and follicles of the 
organ. True miliary tubercle does not seem to occur in 
the prostate. 

The symptoms are those of a severe chronic prostatitis. 
Generally, there is more or less frequency of micturition. 
The symptoms become spontaneously better or worse, but 
the general tendency is toward steady aggravation. The 
cheesy masses ulcerate, form abscesses that break in all 
directions, leaving open cavities or fistulas. Intermittent 
hemorrhage from the urethra is quite a constant symptom. 
The disease is probably more common than has hitherto 
been supposed. 

Character of the Urine. — Quantity. — The twenty-four- 
hour quantity is usually not far from looo c.c. 

Color. — Pale. The freshly passed urine is usually tur- 
bid, and sometimes it is opaque. 

Reaction. — Acid. 

Specific Gravity. — Usually, below the average normal, 
varying between 1012 and 1018. 

Normal Solids. — Both relatively and absolutely, dimin- 
ished, but dependent largely on the extent of the constitu- 
tional disturbance and the appetite. 

Albumin. — This varies as the amount of pus and blood 
present in the urine ; it is usually from a slight trace to a 
large trace. 

Sediment. — This is generally abundant and consists 
chiefly of pus both free and in clumps ; a large number 
of small round cells, some of Avhich are fatty ; often an 
excess of dense round cells from the neck of the bladder 
and prostatic urethra ; and a few (sometimes numerous) 
blood globules. When the freshly passed urine is examined, 
the pus is often found to be ameboid. Large clumps of 
degenerated and disintegrated pus and cells are occasion- 
ally found. 

A urine having the above characteristics should always 
be examined for tubercle bacilli, which, however, are usu- 
ally difficult to find, but occasionally they are present in 



CANCER OF THE PROSTATE. 359 

large numbers. (For details concerning the examination 
for tubercle bacilli, seep. 325.) If the bacilli are not found 
in the sediment after repeated trials, a guinea-pig should be 
inoculated with a portion of the sediment in order to deter- 
mine positively their presence or absence. 



CANCER OF THE PROSTATE. 

Primary cancer of the prostate is exceedingly rare. It is 
usualty secondary to carcinoma or sarcoma elsewhere, es- 
pecially in the kidney or testicle. The scirrhous, melanotic, 
and medullaiy forms have all been noted ; of these the latter 
is perhaps the most frequent. 

The symptoms at first are those caused by an in- 
crease in the size of the organ, such as obstruction to 
the outflow of urine, frequency of micturition, and pain. 
The early symptoms are not pathognomonic. Later in 
the disease the cancerous cachexia, glandular enlargement, 
and the evidences of a cancerous affection elsewhere in the 
body are usually sufficiently prominent to suggest cancer 
of the prostate. Rectal examination may be of value in 
determining the form of cancer that exists. Hematuria is 
common. 

Urine. — An analysis of the urine is often of but little 
value in the diagnosis of cancer of the prostate. The charac- 
teristics of the urine are usually those of chronic prostatitis. 
The urine may, from time to time, contain a large amount of 
blood. Occasionally, the presence of a large number of 
medium and small round cells, with relatively large and 
prominent nuclei, may suggest the presence of malignant 
disease of the prostate. 

The diagnosis of cancer of the prostate is very difficult 
if the disease appears after the organ has from any cause 
become hypertrophied. 



URETHRITIS. 

Of all the diseases encountered in genito-urinary surgery 
urethral inflammation is the most common. Although 
strictly a local affection, and exerting little or no poisonous 
action upon the blood, it is the most venereal of all venereal 
diseases, since it is the commonest malady acquired during 
the copulative act. 



360 DISEASES OF THE URINARY TRACT. 

The term tirethritis signifies simple inflammation of the 
urethra. The term gonorrJiea, although etymologically 
inaccurate, indicating as it does a flow of semen, has been, 
and is still, universally employed and considered, especially 
among the laity, to have the same meaning as the term 
urethritis. But a gonorrhea is in all probability due to a 
specific organism — the gonococcus. A gonorrhea is a ure- 
thritis, but the converse is by no means always true, since 
urethral inflammation may have a variety of causes other 
than an infection with the gonococcus. For practical pur- 
poses it is better to retain the two terms, calling that gonor- 
rhea that has been unmistakably derived from an individual 
of the other sex with a gonorrhea, and reserving the term 
urethritis for all inflammatory urethral discharges having 
another origin. Or the term simple iiretJiritis may be used 
to indicate those conditions in which the gonococcus is 
absent, and specific urethritis to indicate those in which the 
gonococcus is present. 

Causes. — Simple Urethritis. — Authentic cases are on 
record of well-marked urethritis following exposure to 
leucorrheal discharges ; to the pus from a healthy abscess, 
or from a purulent bronchial catarrh ; to the secretion from 
an endocervicitis or endometritis ; to the discharge result- 
ing from ulceration or malignant disease of the uterus ; to 
menstrual fluid or acrid vaginal discharges ; to power- 
ful injections ; to the irritating influences of crystalline ele- 
ments or the passage of a calculus ; to catheterization ; to 
exposure to cold and wet ; to a concentrated urine ; to 
the action of certain drugs — cantharides ; to the extension 
of inflammatory diseases from the prostate or bladder ; 
occasionally, to the free use of alcoholic drinks, especially 
beer — the so-called *'beer clap" ; and to many other non- 
specific causes. 

Specific Urethritis or Gonorrhea. ^ — There is scarcely 
a shadow of doubt but that the cause of gonorrhea is the 
gonococcus of Neisser. (See p. 268.) The microscopic 
detection of this micro-organism is, so far as known, the 
only safe means of distinguishing between specific urethritis 
and a simple urethritis. 

Prominent Symptoms. — The most constant symptom of 
a simple urethritis is a urethral discharge. On the first, 

1 For details concerning this disease, see special works on genito-urinary 
surgery. 



URETHRITIS. 361 

second, or third day after having indulged in sexual inter- 
course, perhaps with a partner having an extensive leucor- 
rhea, the first symptom noticed is a slight, uneasy sensation 
at the meatus, a little smarting, and a pearly drop of pus at 
the meatus ; or perhaps the lips of the urethra are glued 
together in the morning on rising. The inflammation will 
probably not run high or last long, and upon microscopic 
examination specific gonococci will not be found. In some 
instances the discharge is profuse, the inflammation runs 
high and continues for weeks, and with the exception of 
the absence of gonococci the disease can not be distinguished 
from true gonorrhea. There may be pain all along the 
pendulous urethra, and the canal is sensitive to pressure ; 
the meatus feels hot and sore, and urination is frequent and 
painful. Chordee may be as prominent as in a true gonor- 
rheal inflammation. An acute prostatitis or cystitis may 
follow. General systemic disturbance is sometimes marked. 
Organic stricture may follow a simple urethritis. 

Character of the Urine. — Quantity. — Usually dimin- 
ished — 800 c.c. to 1200 c.c. 

Color. — Normal or high. The urine is generally more 
or less turbid owing to the pus and epithelial cells in sus- 
pension. 

Specific Gravity. — From 1020 to 1030, but dependent 
on the concentration of the urine. 

Reaction. — Usually, strongly acid. 

Normal Solids. — Relatively, normal or increased ; abso- 
lutely^ normal. In those cases in which marked constitu- 
tional disturbance exists the solids are generally absolutely 
diminished. 

Albumin. — Albumin is invariably present ; the quantity 
is dependent on the amount of blood and pus present ; it 
usually varies between \\\^ slightest possible trace and a large 
trace. 

Sediment. — Chiefly dense pus ; many urethral cells 
and an occasional (or few or numerous) blood globule ; 
often an excess of mucin (nucleo-albumin). If the inflam- 
matory process is most marked in the prostatic urethra, 
cells from that region, as well as cells from the neck of the 
bladder, will be found with the pus. In case of an organic 
stricture, or gleet, the pus and cells will be found chiefly in 
shreds of mucin (nucleo-albumin). 

The urine should be carefully watched for evidences of 



362 DISEASES OF THE URINARY TRACT. 

a complicating prostatitis or cystitis, in which case the 
amount of pus will be larger, and the quantity of blood 
greater than in a urethritis. There will also be an unusual 
number of cells from the prostatic region, and, perhaps, 
casts of the prostatic ducts and spermatozoa ; or, in case of 
cystitis, an abundance of squamous epithelium. 

In all cases of urethritis of doubtful origin, a thorough 
search for gonococci should be made, (For method of 
staining, see p. 268.) 

CHYLURIA, 

This is a condition that results from a pathologic commu- 
nication between the lymphatic system and the urinary 









rf'-'^va- ' ""■ 'y-o'st. 













Fig. 54. — The filaria sanguinis hominis. The head can be seen at the left of cut ; 
tail, at the right. The parasite is inclosed within a hyaline capsule. Magnified 



passages. Under such circumstances the urine has a milky 
appearance, due to the presence of chyle. The cause of 
this disease is a parasite — the filaria sangitinis Jiominis (see 
Fig. 54) — that invades the blood and obstructs the lymph- 
atic channels, finally resulting in the rupture of a lymph- 
atic vessel. The disease appears to be confined chiefly to 
the tropics (India, China, Bermuda, Brazil, Australia, and the 
West Indies), or to those individuals who have spent much 
of their lives there. Guiteras has shown that the disease is 
not uncommon in the Southern States. It is of rare occur- 
rence in the New England States, the author having met with 
only five cases ; in two of these cases the filaria was readily 



CHYLURIA. 363 

found in the blood. Besides the endemic form of this dis- 
ease, it is very rarely met with following traumatism and 
disease in which an abnormal communication has formed 
between the lymphatics and the urinary tract. Osier refers 
to a nonparasitic form of chyluria. The disease affects alike 
both males and females, and may occur at any age. 

A peculiar feature of the parasite is that it works at 
night, or while the patient is in the recumbent position, being 
quiescent while the patient is up and about. In conse- 
quence, the night urine is milky, while that passed during 
the day is clear and usually of normal color ; but if the in- 
dividual sleeps or reclines during the day, the urine passed 
at that time is milky. 

Characteristics of the Urine. — The characteristics of a 
ch}4ous urine are as follows : 

Quantity. — This is usually below the average normal — 
1500 c.c; it may, however, be normal or slightly increased. 

Color. — Milky. Opaque. Occasionally, the urine is 
slightly tinged with blood. 

Reaction. — Acid. 

Specific Gravity. — Usually, normal or sHghtly dimin- 
ished ; it maybe as low as loio, particularly if the quantity 
of urine is moderately increased. 

Normal Solids. — Relatively, normal or slightly dimin- 
ished. Absolutely, slightly diminished, especially the urea 
and chlorides. The phosphates may be moderately in- 
creased. 

Albumin. — This will depend chiefly on the amount of 
blood present in the urine. Usually, the quantity varies be- 
tween the slightest possible trace and a trace. Owing to the 
opacity of the urine, the usual tests for albumin can not be 
satisfactorily applied. It is necessary to first remove the fat 
in suspension by shaking with ether ; then either the nitric 
acid or the heat test can be applied to the clear urine in the 
usual manner. 

Sediment. — Slight ; often no sediment is visible on in- 
spection. Chiefly fine granular matter, a few leucocytes, 
and an occasional (or few, and sometimes numerous) blood 
globule. Perhaps, rarely a hyaline and granular cast and 
renal cell may be found. Casts are not always present. No 
fat globules are discernible by the microscope. Often a few 
uric acid crystals may be seen. The filaria has been found 
in the urine, but its presence is, by no means, constant. 



364 DISEASES OF THE URINARY TRACT. 

The fat in a chylous urine is in a complete state of emul- 
sion, and since it can not be seen microscopically, its pres- 
ence is deteruiined with certaijity only by sJiaking with ether. 
The ether takes up the fat and leaves the urine clear and 
of normal appearance. The fat does not separate from a 
freshly passed chylous urine, or one that has been hermeti- 
cally sealed or is sterile — that is, the fat does not rise to 
the surface as in the case of milk. Dr. E. S. Wood has in 
his possession a specimen of chylous urine that he sealed 
up while it was fresh (sterile) in the year 1874. The fat 
has not separated and the specimen has its original appear- 
ance. When, however, a urine containing chyle is allowed 
to stand exposed to the air, it undergoes the usual ammo- 
niacal fermentation and the fat rapidly separates, rising to 
the surface, as in milk. 

Sometimes a chylous urine undergoes spontaneous co- 
agulation on standing ; occasionally, coagulation takes 
place in the bladder, and may give rise to most distressing 
symptoms until it is broken up and removed. The firm, 
vibrating, jelly-like clots that form after the urine is voided 
often resemble corn-starch blanc mange. This characteris- 
tic of a chylous urine is dependent upon the presence of 
fibrin, the quantity of which varies considerably ; usually, 
it is not present in sufficient amount to cause coagulation. 

A chylous urine should always be distinguished from a 
urine to which milk has been added either accidentally or 
intentionally. In such a urine the individual globules of 
fat are readily made out under the microscope, and the fat 
is not separated from the urine by shaking it with ether. 



HEMOGLOBINURIA, 

Hemoglobinuria is a condition that is characterized by 
the presence of blood coloring-matter in the nrine, with veiy 
few, if any, of the corpusadar elements of the blood. This 
condition should in all instances be distinguished from a 
hematuria which indicates the presence of both blood pig- 
ment and corpuscular elements. (See p. 234.) Hemo- 
globinuria is the result of the destruction of the red blood- 
corpuscles within the blood-vessels or tissues ; the blood 
coloring-matter that is then set free finds its way into the 
urine. The blood pigment, as found in the urine under 
these circumstances, is generally in the form of oxyhemo- 



HEMOGLOBINURIA. 365 

globin and hematin, although, according to Hoppe-Seyler ^ 
and Halliburton, 2 in some instances the pigment may be in 
the form of methemoglobin (spectroscopic examination). 
Two clinical groups of this condition may be distinguished : 

(a) Toxic Hemoglobinuria. — This is induced by poisons 
that cause rapid destruction of the blood-corpuscles, such 
as carbon monoxide, arseniureted hydrogen, muscarine, 
potassium chlorate (in large doses) ; also the poisons of 
scarlet fever, malaria, yellow fever, typhus fever, purpura 
hemorrhagica, scurvy, and syphilis. It is quite common 
following extensive burns. Exposure to cold and violent 
muscular exercise are stated to produce hemoglobinuria, 
but such instances have not been observed by the author. 
Epidemic hemoglobinuria (Winckel's disease) occurs in the 
new-born. It begins about the fourth day of life, and is 
associated with jaundice, cyanosis, and nervous symptoms. 
This form of disease should be distinguished from sim- 
ple icterus neonatorum, with which there may be blood and 
blood coloring-matter. According to Osier, this condi- 
tion is probably an acute infectious disorder. 

(b) Paroxysmal Hemoglobinuria. — This form of dis- 
ease has been found in persons subject to various forms of 
Raynaud's disease. It is also associated with cold and 
exertion, and has been brought on in susceptible persons 
by the use of a cold foot-bath. This form of hemoglobin- 
uria is not infrequent in malaria. According to Bastianelli, 
it practically never occurs except in infections with the 
estivo-autumnal parasite. This condition should not be 
mistaken for malarial hematuria. 

The attacks may be preceded by chills and fever ; in other 
instances the temperature is subnormal. There may be 
vomiting and diarrhea. Pain in the lumbar region is not 
uncommon. Jaundice has been present in a number of 
cases. The paroxysms rarely persist for more than a day 
or two. Paroxysmal hemoglobinuria is more common in 
males than in females, and occurs chiefly during adult life. 

Character of the Urine. — Quantity. — This is usually 
below the normal. If much fever, the quantity may not 
exceed 500 or 800 c.c. 

Color. — Smoky or dark brown. In extreme cases the 
urine may be black. 

1 Hoppe-Seyler, "Physiol. Chemie.," S. 862. 

2 Halliburton, "Chemical Physiology and Pathology," p. 777. 



366 DISEASES OF THE URINARY TRACT. 

Reaction. — Generally acid ; if the urine is highly con- 
centrated, the reaction may be strongly acid. 

Specific Gravity. — Usually, normal or high — from 1020 
to 1030. 

Normal Solids. — Absolutely, diminished; the degree of 
diminution will depend largely on the disease that causes 
the hemoglobinuria. Relatively, increased or normal. 

Albumin. — This varies between a trace (mild cases) 
and ^ of I per cent, (severe cases). The quantity of 
albumin corresponds to the amount of blood pigment 
present. 

Sediment. — Chiefly brown granular matter, colored by 
the hematin. An occasional, or few, brown and fine gran- 
ular, and often numerous brown granular, casts. Rarely, 
an occasional blood globule. The number of blood 
globules bears no proportion whatever to the intensity of 
the color of the urine. There are usually, also, a few 
brown-stained squamous and renal cells. 

The diagnosis of hemoglobinuria depends upon the dark- 
brown color, the virtual absence of corpuscular blood ele- 
ments, the large quantity of albumin, and the detection of 
blood pigment by means of Teichmann's test (see p. 237) 
or the spectroscope. Hemoglobinuria should always be 
distinguished from hematuria ; it should not be confounded 
with the dark-brown urines seen after the external or inter- 
nal use of carbolic acid, pyrogallic acid, salol, naphthol, and 
other petroleum compounds, in which the color deepens as 
the urine stands exposed to the air, and in which the quan- 
tity of albumin is small. Hemoglobinuria should not be 
mistaken for melanuria, or hemotoporphyrinuria. Spectro- 
scopic examination is usually of value in deciding as to the 
nature of the pigment present. 



PNEUMATURIA, 

The passage of gas with the urine is not a common con- 
dition. Gas may gain entrance to the bladder by the fol- 
lowing means : (i) From mechanical causes, as vesical 
irrigation or cystoscopic examination in the knee-chest posi- 
tion. (2) By developing in the viscus, following the intro- 
duction of gas-forming organisms in catheterization or other 
operations. The yeast fungus, the colon bacillus, and the 
bacillus aerogenes capsulatus have been found. (3) By 



UREMIA. 367 

communication with some air-holding viscus, as in cases of 
vesico-enteric fistula. 

Most cases of pneumaturia occur in old men with enlarged 
prostates, or in case of obstruction from stricture of the ure- 
thra. The passage of the gas is usually at the end of mic- 
turition, and sometimes may be accompanied by a loud 
sound. The diagnosis is readily made by causing the pa- 
tient to urinate while bathing or by plunging the end of 
the catheter in water. 

UREMIA* 

A toxemia developing in the course of nephritis or in 
conditions associated with anuria, usually results in a train 
of symptoms that have received the name uremia. The 
nature of the poison or poisons that produce these symp- 
toms is as yet unknown. 

Many theories as to the cause of uremia have been ad- 
vanced. The view most widely held is that the condition 
is due to the accumulation in the blood of waste substances 
— body poisons — that should be thrown off by the kidneys. 
As Carter has said, '' If, however, from any cause, these 
organs [the kidneys] make default, or if there be any pro- 
longed obstruction to the outflow of urine, accumulation of 
some or of all the poisons takes place, and the characteristic 
symptoms are manifested ; but the accumulation may be 
very slow, and the earlier symptoms, corresponding to the 
comparatively small dose of poison, may be very slight ; 
yet they are in kind, though not in degree, as indicative 
of uremia as are the more alarming symptoms, which ap- 
pear toward the end, and to which alone the name uremia 
is often given." 

Another view is that uremia depends on the products of 
abnormal metabolism. Hughes and Carter concluded, from 
a careful study of this question, that the poison is of an albu- 
minous nature ; in fact, quite different from anything found 
in normal urine. Herter and others have shown that the 
toxicity of the blood-serum in uremic states is much in- 
creased. Brown-Sequard suggested that the kidneys have 
an internal secretion, and it is urged that the symptoms of 
uremia are due to their disturbance. Traube believed that 
the symptoms of uremia, particularly coma and convul- 
sions, were due to localized edema of the brain. 

It is safe to say that we know practically nothing of the 



368 DISEASES OP^ THE URINARY TRACT. 

cause of uremia. Experiments have shown that urea is 
probably not a causative agent ; but how much the other 
urinary salts and the nitrogenous extractives have to do 
with the condition has not yet been determined. Bouchard 
claims to have separated from the urine no less than seven 
different substances that play a part in uremia : 

1 . Diuretic substance : fixed, organic, and in reality urea. 

2. Narcotic substance : fixed, and of organic nature. 

3. Sialogenous substance : organic ; chemic nature un- 
known. 

4 and 5. Two substances causing convulsions : one (4) 
may belong to the group of coloring-matters ; it is in reaHty 
an alkaloid. The other (5) is the potassium salts. 

6. A substance causing contraction of the pupil : fixed, 
organic, and comparable in many respects to the organic 
substance that induces convulsions. 

7. A substance that reduces heat : fixed and organic. 
Bouchard's observations tend strongly to confirm the 

view now generally held that the symptoms are caused by 
the retention of excretory products of the body. It must 
be conceded that the nature of these poisonous ingredients 
is complex. 

Prominent Symptoms. — From a clinical point of view, 
uremia may be either acute or chronic. The division of the 
symptoms as given by the French writers is perhaps most 
practical, and is as follows : {a) cerebral ; (8) dyspneic ; (c) 
gastro-intestiiial. 

Among the cerebral manifestations are (i) mania; (2) 
delusional insanity; (3) convulsions; (4) coma ; (5) local 
palsies ; and a variety of nervous phenomena, such as 
occipital headache, intense itching of the skin, numbness 
and tingling in the fingers, and cramps in the muscles of 
the legs. 

Dyspnea. — This may be paroxysmal or continuous, and 
there may be Cheyne-Stokes breathing. 

The gastro-intestinal manifestations are usually chiefly 
nausea and vomiting ; the latter may be almost uncontrol- 
able. Diarrhea may be present ; sometimes it is profuse 
and associated with an intense catarrhal or even diphtheric 
inflammation of the colon. 

Urine. — An examination of the urine is of the greatest 
value in the diagnosis of uremia. The quantity of urine is 
usually much diminished ; there may be almost complete 



UREMIA. 369 

suppression. On the other hand, the quantity may be nor- 
mal or even increased. In a case of chronic interstitial 
nephritis studied by the author at the Boston City Hos- 
pital, uremic symptoms rapidly developed when, for any 
reason, the quantity fell from 3 500 or 4500 c.c. down to 
2000 c.c. 

The norvial solids are usually diminished, especially 
the urea, but they may be normal or only slightly reduced. 
As a rule, the activity of the symptoms bears an inverse 
ratio to the quantity of urea excreted. Albumin is always 
present in the urine in this condition. It may vary be- 
tween the slightest possible trace and 3 or 5 per cent., but 
the quantity will depend upon the nature of the associated 
lesion. The author has not met with a single instance of 
uremia in which albumin was not present, at least, in the 
slightest possible trace. The sedimeiit invariably contains ab- 
normally formed elements, particularly renal casts and renal 
cells. It may contain a variety of other abnormal elements, 
such as blood, pus, and crystalline elements. Waxy casts 
are very common in the sediment, especially when the 
condition accompanies advanced chronic disease of the 
kidneys. 

Uremia may occur during either an acute or chronic 
kidney disease. An acute exacerbation of a subacute or 
chronic nephritis is very liable to be followed by uremic 
symptoms. So far as the author is aware, uremia never 
occurs during the course of a simple active hyperemia. 

Puerperal eclampsia, a common complication arising 
before, during, or after confinement, in all probability is 
identical with uremia. It may occur in the course of an 
extensive passive hyperemia of pregnancy, or as the result of 
a sudden acute nephritis. A woman who has had a per- 
fectly normal pregnancy may suddenly develop uremia 
(eclampsia) without previous warning either in the urine or 
by physical signs. No doubt puerperal eclampsia is the 
result of a toxemia, and it may have the same cause or 
causes as uremia. 

Diagnosis. — Uremia should, in every instance possible, 
be distinguished from cerebral lesions, such as hemorrhage, 
meningitis, and even tumors; also epilepsy, acute alcoholism, 
opium-poisoning, and diabetic coma. For information re- 
garding the differential diagnosis of uremia, the reader is 
referred to various works on medicine. 
24 



370 THE URINE IN GENERAL DISEASES. 

DIABETES MELLITUS. 

Diabetes mellitus is a disease in which grape-sugar or 
glucose is excreted in the urine for a long period, — often for 
many months or years, — and excreted in large quantity or 
in sufficient amount to give a reaction with the ordinary 
clinical tests for sugar. But the term diabetes mellitus can 
not be applied to all cases in which sugar is detected in the 
urine. Glucose is occasionally present in the urine for a 
short period only, as after febrile attacks, acute diseases, and 
injuries, and as a result of the action of certain toxic sub- 
stances. These are cases of temporary glycosuria, and not true 
diabetes mellitus. Then, again, after a very large quantity 
of saccharine food has been taken a small amount of grape- 
sugar may appear in the urine of many apparently healthy 
persons, or if the sugar in the diet should exceed a certain 
limit, a small quantity of it will always be found in the 
urine ; these are instances of temporary alimentary glycosu- 
ria (Williamson). 

Causes. — Hereditary influences are important ; instances 
are on record of its occurrence in many members of the 
same family. Males are more frequently affected than 
females, the ratio being about three to two ; this is especially 
true after the age of thirty. In the early period of life, and 
before the age of thirty, the liability of the two sexes 
is about equal. The disease may occur in infancy — under 
one year — or in extreme old age. Hebrews are especially 
prone to this disease. It is comparatively rare in the 
colored race (from 8 to lo per cent, Futcher). In most 
of the cases of diabetes after thirty years of age the subjects 
have been excessively /"<3;/ at the beginning of, or prior to, 
the onset of the disease. The so-called " fat man's diabe- 
tes " is not of grave significance, since it is usually the 
result of excesses of starchy and saccharine diet, and is only 
occasionally followed by true diabetes. Von Noorden has 
shown that there may be a '* diabetogenous obesity," in 
which diabetes and obesity develop in early life ; such 
cases are very unfavorable. Gout, syphilis, and malaria 
have been regarded as predisposing causes. Severe nervous 
strain and nervous shock precede many cases. In one 
instance seen by the author a true diabetes followed severe 
fright at the sight of a snake. The combination of seden- 
tary life, close application to business, and overindulgence in 



DIABETES MELLITUS. 371 

food and drink seem especially prone to induce the disease. 
Injuiy to, or disease of, the brain and spinal cord is not in- 
frequently followed by diabetes. In an investigation of 2 1 2 
cases of trmunatic glycosuria by Higgins and Ogden ^ the 
following results were noted : In cases of scalp wounds and 
minor head injuries glycosuria was found in 5.95 percent.; in 
scalp wounds with exposure of bone, 9.3 per cent; in con- 
cussion, 2.5 per cent.; in fractures of the vault of the 
skull, 20.8 per cent.; and in fractures of the base, 23.8 per 
cent. From the examination of these 212 cases the follow- 
ing conclusions were drawn : 

1. That sugar may appear in the urine as early as six 
hours after a head injury, and disappear within twenty-four 
hours ; the average time for its appearance being from eight 
to twelve hours ; the average time for its disappearance 
being from the fifth to the ninth day. 

2. That a small proportion of cases exhibit a permanent 
glycosuria from the date of the injury to the head. 

3. That acetone and diacetic acid are rarely, if ever, found 
in such cases, excepting when the condition becomes a per- 
manent glycosuria, and even then probably only after a 
number of months or years. 

Glycosuria may occur during pregnancy. An irritative 
lesion of Bernard's diabetic center in the medulla is an occa- 
sional cause. Glycosuria sometimes occurs during the 
course or following acute infectious diseases. 

Hibbard and Morrissey ^ found in the observations made 
on 230 diphtheria cases that glycosuria was present in 25 
per cent, of all cases examined ; in 17 per cent, of the fatal 
cases, and in 19 per cent, of those that recovered. The 
quantity of sugar in these cases varied between a mere trace 
and 3 y^ per cent. The time of the appearance of the 
glucose in the urine varied from the second to the eighteenth 
day, and the duration varied from one day to several weeks. 
The authors concluded that, in many instances, antitoxine 
was the probable cause of the glycosuria. 

A glycosuria sometimes makes its appearance just before 
death in cases of chronic diffuse nephritis and subacute 
glomerular nephritis. It appears to be in some way con- 
nected with the extensive dropsy at this time, and is, per- 
haps, the result of edema of the brain. 

1 "Boston Medical and Surgical Journal," Feb. 28, 1895. 

2 "Journal of the Boston Society of Medical Sciences," Feb., 1898. 



372 THE URINE IN GENERAL DISEASES. 

Lesions of the pancreas are met with in about 50 per cent, 
of the cases (Hansemann). Total extirpation of this organ 
in dogs has been shown by v. Mering and Minkowski to pro- 
duce diabetes ; the same result follows the complete removal 
of the pancreas in man. In disease of the pancreas diabetes is 
supposed to be caused by the prevention of the formation 
of the glycolytic ferment. It is believed that this ferment, 
which emanates from the pancreas, is taken up by the blood, 
and that it is by its presence alone that the normal assimi- 
lative processes can take place W'ith the glycogen. 

The nature of diabetes mellitus is unknown. For a sum- 
mary of the anatomic changes found in this disease, the 
reader is referred to Saundby's *' Lectures on Diabetes," 
1891. 

Character of the Urine. — Quantity. — This is usually 
greatly increased, the increase being generally in direct ratio 
to the quantity of sugar present. In the average case the 
quantity varies from 3000 c.c. to 6000 c.c. In very severe 
cases it may go as high as, or even exceed, 10,000 or 
20,000 c.c. in twenty-four hours. Occasionally, the total 
daily quantity is less than 1500 c.c. This is particularly 
true in the very mild forms of temporary glycosuria, or near 
the fatal termination of cases of true diabetes mellitus. 

Color. — Usually, very pale. Watery. Sometimes the 
urine has a normal, or rarely a high, color. On standing 
diabetic urine speedily becomes opalescent, owing to the 
rapid development of yeast spores and other fungi. 

Reaction. — Generally acid. It is often strongly acid, 
and the acidity increases at the onset of diabetic coma 
(Williamson). When a diabetic urine is allow^ed to stand, 
it remains acid for many days, and it may even increase in 
acidity, owing to the development of lactic acid by ferment- 
ation. 

Specific Gravity. — This is increased ; it generally ranges 
between 1025 and 1 050, or it may be higher still. Not in- 
frequently the specific gravity is below 1020. While the 
density of the urine is raised if a large quantity of sugar be 
present, we can not conclude, if the specific gravity be low, 
that sugar will be absent ; the urine should be tested foi^- sugar 
in every instajtce, whether it has a high or a low specific 
gravity. 

Normal Solids. — Absolutely, increased, or they may be 
normal. Occasionally, the total urea goes as high as 60 or 



DIABETES MELLITUS. 373 

100 grams. 1 Owing to the large quantity of urine, the 
normal solids are relatively diminished. In very mild cases 
with a small quantity of sugar they may be relatively 
normal. 

Preceding or during diabetic coma the normal solids are 
usually both relatively and absolutely diminished. 

Under ordinary conditions the total solids of the urine are 
high, owing to the presence of the sugar. 

Sugar. — The presence of sugar is, of course, the most 
important abnormality of the urine in diabetes. The per- 
centage varies, according to the nature of the case, from 
0.5 up to 8 or 12. The daily quantity of sugar also varies. 
It is often from 20 to 60 grams in the twenty -four hours, but 
may rise to 300 or 500 grams. In rare instances the total 
quantity of glucose may exceed 750 grams. 

To estimate the amount of sugar, the total quantity of 
urine for twenty -four hours must be carefully collected and 
well mixed, and then a sample submitted to examination. 
The twenty-four-hour excretion of sugar should be calcidated 
in all cases, since it is by this means only that definite infor- 
mation regarding the effect of treatment is obtained. 

The twenty-four-hour quantity of urine should always be 
accompanied by a specimen of the fasting urine (early morn- 
ing urine) ; also by a specimen passed after the heartiest 
meal. A very small amount, or an entire absence, of sugar 
in the fasting urine constitutes an important element in the 
diagnosis between a temporary glycosuria and a true dia- 
betes mellitus. 

Albumin. — This is usually present, but in very small 
amount — generally the slightest possible trace. In case there 
is a coexisting chronic interstitial nephritis, which is not 
very common, the amount of albumin may reach a trace or 
large trace. 

Sediment. — An occasional hyaline and finely granular 
cast ; rarely a renal cell and blood globule. There is 
usually, also, a moderate excess of squamous epithelium 
and sometimes a slight excess of leucocytes. If the urine 
has been allowed to stand for some period, an abundance 
of sugar spores (torula cerevisiae) will be found. 

The nature of the renal disturbance in the majority of 
cases of diabetes mellitus is a renal congestion (active hy- 
peremia), which is probably partly caused by the irritating 
action of the sugar on the renal epithelium, and possibh' by 

^ See p. 56. 



374 THE URINE IN GENERAL DISEASES. 

the ingestion of an unusual amount of nitrogenous food. 
But a chronic nephritis (usually the interstitial form) is 
sometimes met with, especially in those cases of permanent 
diabetes that have been in progress for several years. Un- 
der these circumstances the quantity of albumin is some- 
what higher, the number of casts larger, and the normal 
solids lower than in the average case of diabetes attended 
with a renal congestion. 

Prominent Symptoms. — /;/ temporary glycosuria symp- 
toms may be slight or entirely wanting. Usually, polyuria 
is the most noticeable sign of the condition. A hearty ap- 
petite and gastric disorders are not uncommon. A craving 
for sweets is sometimes present. The patients are, as a 
rule, obese and past the age of thirty. Occasionally, the 
symptoms in this form quite closely resemble those asso- 
ciated with true diabetes mellitus, but usually the)^ are 
milder than in the permanent form of the disease. 

In peinnanent diabetes the most prominent symptoms are 
(i) a constant and seemingly unquenchable thirst, (2) poly- 
uria, (3) hunger, (4) emaciation, (5) general weakness, and 
(6) a variety of nervous disorders. Although the quantity 
of water taken is frequently excessive, the tongue and mouth 
remain dry, parched, and congested. Sometimes the gums 
are tender and become shrunken so that the teeth loosen ; 
frequently, the saliva is scanty. The skin is dry and harsh. 
Eczema and erythema, especially about the genital organs, 
are frequent and annoying symptoms. Boils and carbuncles 
are among the most common of the skin lesions in diabetes. 
They often occur at an early stage, and sometimes are the 
first symptoms noticed by the patient. 

The temperature may be normal or subnormal. In ad- 
vanced cases, and especially preceding or during diabetic 
coma, the temperature may be as low as 95° or 94° F. 
As a result of the voracious appetite, the digestion sooner 
or later becomes disordered. Constipation and attacks of 
diarrhea are not uncommon ; constipation is the rule. 

Various nervous manifestations appear, such as neuralgia, 
neuralgic pains in the chest, pain and tenderness in the 
calves of the legs (neuritis), sometimes sufficient to inter- 
fere with walking. Sensations of abnormal heat of the 
skin are common. The patient becomes fretful, irritable, 
and hypochondriacal, and usually there is a marked lessen- 
ing or a complete loss of sexual power. Gangrene of the 



DIABETIC COMA. 375 

extremities is common, especially in those past the age of 
from thirty to forty years. Cataract and diabetic retinitis 
are liable to occur. 

The pronounced and persistent polyuria produces fre- 
quent micturition, which harasses the patient both day and 
night. The quantity of urine passed during the day usu- 
ally exceeds that passed at night. One of the most 
frequent lung complications is tubercular disease, which is 
most common in poor, hard-working people. Cardiac 
weakness and enlargement, sometimes attended by valvular 
disease or functional disturbances, are not uncommon. 

Diagnosis. — An effort should be made in all cases 
to distinguish between a pcrniaiicnt diabetes mellitus and a 
temporary glycosuria. In both forms the sugar eliminated 
must be glucose (grape-sugar). In the former the sugar is 
constantly present in the urine, while in the latter the fasting 
urine (early morning urine) is generally free from sugar, or 
contains only a very slight trace, and the after-meal urine is 
highly saccharine. A diet free from carbohydrates will 
often serve to distinguish between these two forms, since in 
a temporary glycosuria the urine is usually quite readily 
rendered sugar-free, while in the permanent form the quan- 
tity of sugar may be reduced, but the urine is made sugar- 
free only with great difficulty, or not at all. 

Course and Prognosis. — In children the disease is rapidly 
fatal. It may be stated that the older the patient at the 
time of the onset, the slower the course. In fleshy elderly 
individuals, the disease is much more amenable to treat- 
ment than in thin persons. Cases without hereditary influ- 
ences are the most favorable. Persons are met with who 
have had the disease for fifteen years (Osier). In true dia- 
betes mellitus instances of cure are rare. Not a few of the 
cases of reputed cures belong to the class of temporary 
glycosuria. In cases under thirty to forty years of age the 
outlook is bad. 

DIABETIC COMA. 

Apart from coma produced by various conditions, such 
as cerebral hemorrhage, uremia, etc., there is a special group 
of symptoms ending in coma that is a frequent termination 
of diabetes. These symptoms are unaccompanied by any 
gross lesions of the organs, and are apparently due to the 
toxic condition of the diabetic blood. Generally, the patient 



376 THE URINE IN GENERAL DISEASES. 

comes under treatment for other symptoms of diabetes 
before the onset of the coma ; occasionally, the patient is 
first seen during the comatose stage. 

Diabetic coma occurs both in the severe and mild forms 
of diabetes, and rarely, if ever, in a temporary glycosuria. 
It may occur at any age, but it is very common in young 
persons and in persons under middle life. 

An exciting cause is sometimes a long railway journey. 
A sudden change of diet — from a mixed to a rigid nitrog- 
enous diet — often appears to be an exciting cause of dia- 
betic coma ; and it is said that a sudden change from a 
rigid nitrogenous diet to a mixed nitrogenous and carbo- 
hydrate diet has occasionally been immediately followed by 
coma. The opinion is gradually gaining ground that a highly 
nitrogenous diet favors the development of coma, especi- 
ally in the severe cases in which the urine gives a port- wine 
color with ferric chloride (diacetic acid reaction). In many 
instances prolonged constipation has appeared to play some 
part as an exciting cause, but it is not invariably present. 

Diabetic coma appears to be occasionally precipitated by 
intercurrent affections or complications, such as bronchitis, 
pleurisy, pneumonia, tonsillitis, carbuncles, pharyngeal, 
ischiorectal, or alveolar abscesses. The administration of 
anesthetics and the performance of surgical operations have 
also figured occasionally as exciting causes of coma. Rapid 
.and marked loss of weight sometimes precedes the onset of 
coma,. 

The symptoms often begin with lassitude, epigastric 
pain, nausea, and sometimes vomiting. Frequently, dyspnea 
and headache are early symptoms. The patient becomes 
anxious, restless, or excited. Speech becomes thick and 
incoherent, and finally he becomes drowsy, and the drowsi- 
ness gradually develops into coma. The pulse is rapid and 
the tension is low ; the heart's action is weak, but cardiac 
murmurs are not usually heard. The tongue is dry and 
red, and the face becomes pale and cold ; frequently there 
is slight cyanosis. 

Generally, the breath has a peculiar odor ; the urine also 
has the same smell. The latter has been variously de- 
scribed, most frequently perhaps as an odor resembling 
new-mown hay ; it has been termed the acetone odoj\ Con- 
vulsions, as a rule, do not occur, and in this respect diabetic 
coma differs markedly from uremia. 



DIABETES INSIPIDUS. 377 

Bremer's blood test with methylene-blue will often 
serve to distinguish diabetic coma from other forms of 
coma. 

Urine. — The urine is diminished in quantity preceding 
and during diabetic coma, the color is not so pale and the 
acidity of the urine is increased. There is frequently a 
marked diminution in the quantity of sugar before the 
onset and during the coma. Usually, the quantity of 
albumin increases. The normal solids become absolutely 
much diminished. The sediment usually contains numer- 
ous hyaHne and finely granular casts ; a few renal cells, 
which are often quite granular ; and an occasional blood 
globule. 

The urine almost invariably gives the reactions for acetone, 
diacetic acid, and /S-oxy butyric acid. (See pp. 175, 177, 
and 178.) 

Importance of Acetone, Diacetic Acid, and /5-oxy- 
butyric Acid in Diabetic Urine. — Acetone, diacetic acid, 
and /5-oxybutyric acid are most commonly found in the 
urine of the advanced cases of true diabetes mellitus. In 
most instances their presence is an important prognostic 
element. Although the reactions for acetone, diacetic acid, 
and /5-oxybutyric acid may be obtained in the urine for 
weeks or months without any comatose symptoms occurring, 
they certainly indicate the constant danger of coma. The 
author's experience leads him to believe that when these 
reactions are obtained, and especially a marked reaction with 
ferric chloride (diacetic acid), an unfavorable prognosis is 
warranted, although in rare instances he has known both 
acetone and diacetic acid to disappear from the urine as the 
patient improved under treatment. He has never met with 
these two substances in cases of temporary glycosuria. 



DIABETES INSIPIDUS. 

This disease is characterized by the elimination of very 
large quantities of nonsaccharine urine of low specific 
gravity. Willis, in 1674, first recognized the distinction 
between the saccharine and nonsaccharine forms of dia- 
betes. The disease is most common in young persons — 
between five and thirty years of age. Males are more fre- 
quently attacked than females. The affection may be con- 
genital, and in a few instances a hereditary tendency has 



378 THE URINE IN GENERAL DISEASES. 

been noted. Traumatism, such as injury to the head, 
trunk, or limbs, has occasionally been the exciting cause. 
The disease has also followed sunstroke, or violent emotion, 
such as fright ; also intracranial growths or other lesions of 
the nervous system. It has followed rapidly the copious 
drinking of cold water, or a drinking-bout ; or has set in 
during the convalescence from acute disease. Osier has 
noted it in several cases of tuberculous peritonitis. 

Practically nothing is known of the pathology of this 
disease. It is, doubtless, of nervous origin. 

Prominent Symptoms. — The most prominent symptoms 
of this disease are the marked and never-satisfied thirst, 
the elimination of enormous quantities of urine, marked 
emaciation, and a dry, pinched, and dusky skin. Excep- 
tionally, the disease does not appear to interfere in any way 
with the general health. The appetite is usually not in- 
creased as in diabetes mellitus. Death may take place from 
some intercurrent affection. Spontaneous cure may take 
place. 

Character of the Urine. — Quantity. — This varies be- 
tween 5000 c.c. and 20,000 c.c. during the twenty-four 
hours. 
. Color. — Very pale. Watery. 

Reaction. — Faintly acid or neutral. Upon standing, the 
urine soon becomes ammoniacal and turbid, and often has 
a rather offensive, fish-like odor. 

Specific Gravity. — This is very low — usually between 
1 00 1 and 1005. 

Normal Solids. — Absolutely, very much increased ; the 
total urea may exceed 100 grams, while the chlorides, phos- 
phates, and sulphates are also very high. Relatively, very 
much diminished. 

Albumin. — Usually absent ; the urine may, however, 
contain the slightest possible trace of albumin, particularly in 
cases of long standing. 

Sediment. — Very slight. Generally, it is necessary to 
centrifugalize the urine in order to get any visible sediment. 
It usually consists chiefly of cellular elements — squamous 
epithelium and small round cells ; sometimes a leucocyte 
and blood globule are found. In exceptional cases renal 
casts (pure hyaline) may be found. 

Diagnosis. — Hysteric polyuria may sometimes simulate 
this disease very closely. The amount of urine excreted 



DIABETES INSIPIDUS. 379 

may be enormous, but there is never a marked increase of 
the soHds, and often only the development of other hys- 
teric manifestations may enable the diagnosis to be made ; 
a polyuria from this cause is, however, always transitory. 

In certain cases of chronic i?itcrstitial nephritis a very large 
quantity of urine of low specific gravity may be passed, but 
the usual low total solids, the presence of albumin and of 
hyaline casts, and the existence of heightened arterial ten- 
sion, stiff arteries, and hypertrophied left ventricle aid ma- 
terially in the diagnosis. Occasionally, in chronic interstitial 
nephritis the normal solids as well as the quantity of urine 
are very high, as in a case seen by the author about four 
years ago ; a child, age seven ; quantity of urine, from 
6000 to 7000 c.c; specific gravity, from 1002 to 1006 ; urea, 
45 grams ; chlorine, 13 grams ; PgO., 5. 5 grams. On account 
of the absence of the usual signs and symptoms of chronic 
interstitial nephritis the case was supposed to be one of dia- 
betes insipidus, but at the autopsy very small, red, granular 
kidneys were found. 

The course of diabetes insipidus depends entirely upon 
the nature of the primary trouble. Sometimes with organic 
disease, either cerebral or abdominal, the general health is 
much impaired. In the idiopathic cases the affection has 
been known to persist for fifty years with a fair degree of 
health. Death usually results from some intercurrent affec- 
tion. Recovery may take place. 



CHAPTER XL 

THE URINE IN DISEASES OUTSIDE OF THE 
URINARY TRACT. 

FEVER URINE, 

In acute febrile conditions the characteristics of the urine 
become modified from the normal according to the height 
and character of the fever and the degree of toxemia or 
altered metabolism. During the early stage of an acute 
febrile disease the quantity of urine is abnormally small, — 
from 500 c.c. to lOOO ex., — the color is high, there is a high 
specific gravity, and an intensely acid reaction. There is 
usually a considerable amount of sediment ; often there is 
an abundant sediment after the urine cools, due to a deposit 
of amorphous urates. The normal solids are both relatively 
and absolutely increased, especially the urea, which has 
been known to be as high as 85 grams in twenty-four hours. 
Uric acid is also usually increased, although the extent to 
which it is increased is largely dependent on the disease that 
causes the fever. The chlorides are always absolutely dimin- 
ished. The phosphates are absolutely diminished at first, 
but later they are increased. In a very mild febrile attack 
albumin may be absent. In the more severe febrile diseases, 
with high temperature, albumin is always present, vary- 
ing in amount from the slightest possible trace to a trace. 
The sediment usually contains an occasional (or few) gran- 
ular and brown granular cast, some with blood and renal 
cells adherent ; a few (or numerous) free renal epithelial 
cells ; and a few blood globules. 

As the fever begins to abate, the quantity of urine in- 
creases, and frequently there is polyuria during the conva- 
lescence from the febrile condition. Although during con- 
valescence the patient may be taking more food than in 
the early stage of the disease, the normal solids for the 
twenty-four hours will be diminished, owing to the fact that 

380 



URINE OF CHRONIC DISEASE. 381 

the food elements are used to build up those tissues that have 
been diseased. As complete convalescence approaches, the 
quantity of urine falls to the normal, and the solids 
gradually rise to their normal quantities. During conva- 
lescence the albumin and the other abnormal elements grad- 
ually disappear from the urine, and the renal tubules become 
restored to their normal condition. 

In case the acute disease terminates fatally during the 
acute stage the quantity of urea and other solids, instead of 
being high, will be found to gradually diminish up to the 
time of death, and may, on the last day or two of the 
disease, amount to only 5 or 10 grams in twenty -four 
hours. 

The characteristics of the urine in acute febrile condi- 
tions, as a rule, conform to those of an active hyperemia, 
which may be either mild or severe. Such renal disturb- 
ance is no doubt partly due to the irritating action of the 
concentrated urine itself, but is more directly dependent on 
the elimination of irritating toxines developed during the dis- 
ease from which the patient is suffering. Although the 
renal affection usually begins as an active hyperemia, it 
often becomes intensified, and may result in an acute neph- 
ritis. The extent of the renal involvement is usually in 
direct proportion to the degree of toxemia. 

/;/ acute diseases attended with a serous exudation the char- 
acteristics of the urine differ somewhat from the preceding. 
The chlorides are diminished to a much greater extent than 
in an ordinary acute affection without exudation, and, in- 
deed, they may be absent. The urea is also not so high 
(although it may still be above the normal) as in acute dis- 
ease without serous exudation. In rare instances the total 
urea may be considerably diminished, apparently as a result 
of the exudation. (See Pneumonia, p. 385.) 

URINE OF CHRONIC DISEASE (NOT RENAL). 

In many chronic affections of the body in which fever is 
absent, such as cancer, tuberculosis, etc., the urine gener- 
ally has an entirely different appearance from that found in 
acute febrile diseases. 

The quantity is slightly below the normal — 1000 c.c. or 
1200 c.c. ; the color is usually pale, but it may be normal 
or, rarely, slightly high ; the reaction is faintly acid, or it 



382 DISEASES OUTSIDE OF THE URINARY TRACT. 

may be alkaline. The normal solids are both relatively and 
absolutely diminished, the amount of diminution being depen- 
dent largely upon the appetite, which is generally more or 
less disturbed. Albumin is usually present, but in very 
small amount ; occasionally, it is absent. The sediment is 
liable to contain a very few formed renal elements (casts 
and renal cells), although they, too, may be absent. It 
is, however, the rule to find, at least, evidences of a renal 
congestion (active hyperemia), and sometimes coexisting 
primary kidney disease. 



TYPHOID FEVER* 

The quantity of urine is diminished — 500 c.c. to 800 
c.c; the color is very high (absolute increase of the pig- 
ments) ; the reaction is strongly acid ; the specific gravity 
is usually very high — 1030 to 1040 ; the normal solids are 
relatively increased. If, on the other hand, the patient has 
been given a large amount of water or other liquid, the 
quantity of urine will be nearer the normal and it will have 
a normal or pale color and a normal or low specific gravity. 
During the first week of the disease the solids, except the 
chlorides and phosphates, are absolutely increased, the 
former being only slightly diminished while the latter are 
usually much diminished. The quantity of urea may go as 
high as 60 to 70 grams. The uric acid is also much in- 
creased, and the urine not infrequently contains a heavy de- 
posit of amorphous urates. Albumin is almost always 
present ; the quantity varies from the slightest possible trace 
to i/^ of I per cent., the amount being dependent on the 
height of the fever, the toxemia, and the nature of the re- 
sulting renal affection. The sediment is almost certain to 
contain renal casts, an excess of renal epithelial cells, and a 
variable quantity of blood — usually a small amount. 

An active hyperemia that is more or less severe is the 
rule in typhoid fever. Sometimes a genuine acute nephritis 
develops at the onset or during the height of the disease, 
masking in many instances the true nature of the primary 
malady ; in such cases the prognosis is always to be con- 
sidered grave. An acute nephritis developing during con- 
valescence from typhoid fever is quite common, but, as a 
rule, not so serious as when it develops early in the dis- 
ease ; it usually makes its appearance after the fall of the 
fever. Convalescence from an acute nephritis, which has 



YELLOW FEVER. 383 

developed late in typhoid, is usually slow, but complete 
recovery is the rule. 

Pyuria is a common complication of the disease. The 
pus is the evidence of a cystitis or a pyelitis, and in the 
experience of the author the latter is the more common. 
Under these circumstances the urine invariably has the 
characteristics of a chronic cystitis or chronic pyelitis, and it 
usually contains a large number of typhoid bacilli. (See 
p. 268.) Orchitis is occasionally met with during convales- 
cence ; it is usually associated with a catarrhal urethritis. 
In pyelitis, cystitis, or urethritis from this cause treatment 
with the formaldehyde compound known as urotropin is 
usually highly satisfactory. 

In the urine of typhoid fever the diazo reaction of Ehrlich 
is often obtained. (See p. 186.) The clinical value of the 
reaction is doubtful ; it is certain that its value is lessened 
by its occurrence in acute miliary tuberculosis and various 
other diseases associated with high fever. 



YELLOW FEVER. 

The quantity of urine is much diminished from the first. 
The color is high or dark, depending upon the amount of 
blood present ; rarely, it is bloody. The specific gravity is 
usually below the normal, but it may be high. The urea is 
often relatively diminished, but it may be normal ; abso- 
lutely, it is much diminished ; sometimes it is totally absent 
(Purdy). Although there is, without doubt, an increased 
production of urea during the stage of fever, yet, according 
to Cunnisset, the elimination of urea is always less than 
normal, the degree of diminution being in direct proportion 
to the danger of the disease, and affording an important 
element in prognosis. The chlorides are usually both rela- 
tively and absolutely diminished. Albuminuria is regarded 
by Guiteras as the third characteristic symptom of the 
disease. In the mild cases the amount of albumin is 
usually small, but in the severe cases the quantity of 
albumin is large and there may be numerous tube casts of 
various kinds, renal epithelium, an abundance of blood, and 
all the evidences of a severe acute nephritis. Or perhaps 
complete suppression of the urine may supervene, and 
death may occur in uremic convulsions or coma within 
twenty-four or thirty hours. When albumin is present in 



384 DISEASES OUTSIDE OF THE URINARY TRACT. 

the urine on the first day of the disease and continues on 
the second day, Guiteras states that it indicates a severe 
case. The urine frequently contains bile. 



TYPHUS FEVER. 

In this disease the urine is scanty in amount and highly 
febrile. It is highly colored and strongly acid. Occasion- 
ally, it is alkaline, and has a very offensive odor. Relatively, 
the urea is increased ; absohitely, much diminished ; leucin 
and tyrosin may take the place of the urea, as in acute 
yellow atrophy of the liver. The uric acid is relatively in- 
creased, and it may be absolutely increased, especially 
during the early stages of the disease. The chlorides are 
both relatively and absolutely greatly diminished, and may 
be absent. xA^lbumin is invariably present, but usually in 
small amount, except in the severe cases attended with acute 
nephritis. Under such circumstances the urine is bloody 
and bears the other characteristics of an acute nephritis. 
(See p. 296.) The proportion of cases in which an acute 
nephritis occurs varies much in different epidemics ; its ex- 
istence, however, adds decidedly to the gravity of the case. 
A true hemoglobinuria may be seen in the severe cases. In 
the mild cases the characteristics of the urine are those of 
a severe active hyperemia or renal congestion. The sedi- 
ment contains numerous hyaline and granular casts and 
renal cells ; also a varying amount of blood. At the time 
of the crisis copious amounts of urine of low specific gravity 
and pale color are passed. Retention of urine is of fre- 
quent occurrence ; the region of the bladder should be 
frequently examined, and the catheter used if required. 



RELAPSING FEVER. 

In relapsing fever the urinary system is the seat of varjang 
morbid conditions, some of which are of great importance in 
determining the prognosis. Albuminuria is present in a very 
large number of the cases, and is not necessarily a cause of 
very serious alarm. When, however, an abundant excretion 
of albumin is accompanied by the presence of large numbers 
of renal casts, renal cells, and much blood, the prognosis is 
grave. The affection of the kidneys may vary from a 
simple congestion to an actual acute nephritis, the latter 



PNEUMONIA. 385 

being sometimes hemorrhagic in character. Complete sup- 
pression of urine is sometimes present. Hematuria may be 
profuse and exhausting ; it is a grave compUcation and is 
often followed by a fatal issue. Glycosuria has been 
observed during the course of some cases. 



PNEUMONIA. 

Early in the disease the urine presents the usual charac- 
teristics found in acute febrile conditions attended with 
exudation. The quantity of urine is very small — often less 
than 500 c.c. ; the specific gravity is high — 1030 to 1040; 
the color is very high, the amount of pigment being both 
relatively and absolutely increased. The quantity of urea 
is increased. In some instances the urea is diminished 
after the first few days of the disease ; such cases are 
usually characterized by delayed convalescence, diarrheal 
attacks, tuberculosis, pleurisy with effusion, empyema, etc. 
The uric acid is usually very much increased, especially 
just after the crisis, and very often the urine contains a 
very heavy deposit of amorphous urates, and is colored a 
carmine, deep red, or brown. 

The chlorides are very much diminished and may be 
entirely absent, especially between the third and fifth days 
of the disease. The reappearance of the chlorine is evi- 
dence of beginning convalescence — the beginning of the 
absorption of the serous exudation from the diseased lung. 
The chlorine always reappears or commences to increase, in 
quantity before evidences of beginning convalescence can be 
made out by auscultation and percussion or by a fall in the 
temperature. 

Albumin is invariably present in pneumonia — often only 
the slightest possible trace in mild cases, and a large trace to 
^ of I per cent, in the severe cases. Sometimes a large 
amount of albumin and a bloody or smoky urine indicate 
the presence of an acute nephritis. In a large proportion 
of all cases the albumin is evidence of a more or less severe 
toxic condition. According to v. Jaksch, the appearance of 
peptone in the urine is indicative of the beginning of resolu- 
tion. 

The sediment usually contains a few (or numerous) hya- 
line, fine, and brown granular casts, numerous renal cells, 
and abnormal blood globules. Blood may be present in 
25 



386 DISEASES OUTSIDE OF THE URINARY TRACT. 

abundance, when the sediment usually has the other char- 
acteristics of an acute diffuse nephritis. (Compare p. 296.) 

The urine may contain bile pigment. 

During convalescence from pneumonia the quantity of 
urine increases and may exceed the normal ; the quantity 
of urea and uric acid return to, and sometimes fall below, 
the average normal, while the chlorides gradually become 
increased, finally returning to normal. 



PULMONARY TUBERCULOSIS. 

In the average uncomplicated case of pulmonary tuber- 
culosis the urine does not present any special peculiarities. 
The quantity is usually diminished, especially if there is 
fever ; if no fever, the quantity may be increased, even in 
uncomplicated cases. If amyloid infiltration be present as 
a complication, the quantity of urine is usually increased. 
In the average case of pulmonary phthisis with fever the 
color of the urine is higher than normal, the specific gravity 
is moderately increased, and the reaction is strongly acid. 
The normal solids are relatively increased ; absolutely, dimin- 
ished. The urea is usually diminished, but the extent of 
the diminution is dependent on the appetite, the general 
metabolism, and the fever. The uric acid is generally 
increased, while the sulphates are only moderately dimin- 
ished. The chlorides are usually somewhat diminished, 
but the quantity of chlorine is largely dependent on the 
character of the food taken. If there is marked diarrhea, 
the chlorides will be found absolutely very much dimin- 
ished. In some cases of pulmonary tuberculosis the phos- 
phates are absolutely increased, especially when the lung 
tissue is breaking down rapidly. 

Albumin is probably present in the urine of every case 
of advanced phthisis. As has been stated, subacute glomer- 
ular nephritis and amyloid infiltration are frequent compli- 
cations of pulmonary tuberculosis. (See pp. 303, 320.) 
Under such circumstances the quantity of albumin is large. 
If such complications are not present, the quantity of albu- 
min is usually small — slightest possible trace to a trace. 

The sediment usually contains an occasional (or a few) 
renal cast, renal cell, and a very small amount of blood ; 
in other words, evidence of a more or less marked renal 
congestion. 



MALARIAL FEVER. 387 

Besides the liability of an amyloid infiltration, or a sub- 
acute glomerular nephritis as a complication, tubercular 
ulcerations in the kidney, pelvis of the kidney, or the 
bladder are very likely to occur. Pyuria is then the most 
prominent feature of the urine. In all such cases the 
urinary sediment should be veiy carefully examined for 
tubercle bacilli. 

MALARIAL FEVER. 

During the pyrexia the urine has the usual characteris- 
tics of a fever urine. The quantity is small, the color is 
high, and the specific gravity is increased. After the chill 
and the fever the urine is often increased in amount and of 
low specific gravity. There is always an increase in the 
ehmination of urea during a paroxysm, and Jaccoud has 
noted that this increase commences even before the chill, so 
that careful quantitative estimations of urea will often fore- 
tell the approach of a paroxysm. This increase of the 
urea excretion he observed two hours before the chill in 
quotidian, and six or eight hours before in tertian,, fever. 
He regards the increased urea as a reliable indication for 
the proper time for administering quinine in order to antici- 
pate the chill. During the paroxysm the chlorine is eHmi- 
nated in normal amount. On the days between paroxysms 
both the urea and chlorine are usually diminished. 

The urine usually contains albumin, but generally in 
small amount — slightest possible trace. If an acute neph- 
ritis develops, the quantity of albumin is large — yi to ^ 
of I per cent. The sediment generally contains renal casts, 
renal cells, and a few blood globules. The renal disturb- 
ance is usually of the nature of a renal congestion or active 
hyperemia. 

An acute nephritis in malaria is not very common in 
New England. Thayer, ^ who has recently made a study 
of the urine in malaria at the Johns Hopkins Hospital, 
draws the following conclusions : 

(i) Albuminuria is of frequent occurrence in the malarial 
fevers of Baltimore, occurring in 46.6 per cent, of the cases 
studied. (2) It is considerably more frequent in estivo- 
autumnal infections than in the other forms, occurring in 
58.3 per cent, of these instances against 38.6 per cent, in 

1 ''Amer. Journ. Med. Sciences," Dec, 1898, p. 646. 



388 DISEASES OUTSIDE OF THE URINARY TRACT. 

the regular intermittent forms. (3) Acute nephritis is not 
an unusual complication of malarial fever, having occurred 
in 2.7 per cent, of the cases treated in the wards and 
between i and 2 per cent, of all cases seen at the hospital. 
(4) The frequency of acute nephritis in estivo-autumnal 
fever is much greater than in the regular intermittent forms, 
having been observed in 4.7 per cent, of the cases treated in 
the wards and in 2.3 percent, of all cases seen. (5) The 
frequency of albuminuria and nephritis in malarial fever, 
while somewhat below that observed in the more severe 
acute infections, such as typhoid fever, scarlet fever, and 
diphtheria, is yet considerable. (6) There is reason to believe 
that malarial infection, especially in the more tropical coun- 
tries, may play an appreciable part in the etiology of chronic 
renal disease. 

Paroxysmal hemoglobinuria is sometimes a compHcation 
of malaria. Like an acute nephritis, this complication is 
perhaps more common in the Southern States and tropical 
countries than in New England. Out of several hundred 
cases of malarial fever at the Boston City Hospital, the 
author has only once met with hemoglobinuria. The rela- 
tion of this condition to malaria is not so close as has been 
thought by many writers. Bastianelli asserts that it is 
practically proved that malarial hemoglobinuria occurs only 
in infections with the estivo-autumnal parasite. No doubt 
it has frequently been confounded with malarial hematuria. 

Malarial hematuria of renal origin is sometimes encoun- 
tered, especially in the estivo-autumnal form of the disease. 
In such cases the evidences of tubular disturbance of the 
kidney (casts, renal cells, etc.) is usually very slight 

ERYSIPELAS. 

In this disease the urine is scanty in amount, highly 
colored, and of high specific gravity. Relatively, the solids 
are all increased ; absohitely, diminished, especially after the 
first two or three days of the disease. Albuminuria is 
almost constant ; usually, the quantity of albumin is small, 
varying between a very slight trace and a large trace. A 
true acute nephritis is quite common ; the quantity of albu- 
min may then reach, or even exceed, i per cent. The 
sediment always contains renal casts, usually an excess of 
renal epithelium, and a few (or numerous) blood globules, 



CHOLERA. 389 

both free and adherent to casts. The number of casts and 
cellular elements, and the quantity of blood, may be very 
large, indicative of an acute nephritis. In the experience 
of the author an acute pyelonephritis in erysipelas is not 
uncommon. Chronic pyehtis is sometimes the result of 
the acute pyelitis ; convalescence from this complication is 
usually slow. In case the erysipelas is complicated by 
pneumonia, ulcerative endocarditis, or septicemia, a severe 
acute pyelonephritis is quite sure to follow, and the prog- 
nosis is thereby rendered grave. 

CHOLERA. 

In the first two or three days of this disease — algid or 
collapse stage — the quantity of urine is very small, or 
there may be complete suppression ; the color is normal or 
pale, sometimes smoky ; the specific gravity is either normal 
or diminished ; and the reaction is faintly acid. The urea 
is very much diminished ; this marked diminution is un- 
usual in most acute diseases, and in cholera it is prob- 
ably due to the fact that a large proportion of the urea is 
eliminated with the intestinal discharges. In case of sup- 
pression of urine a considerable amount of urea may be 
eliminated by the sweat glands ; indeed, it is sometimes 
ehminated in sufficient quantity to cause a coating of urea 
on the skin, especially in the axillae and groins. The uric 
acid is also much diminished. The chlorides are very much 
diminished, or they may be absent. The phosphates are, 
like the urea, very much reduced. 

The indoxyl — indoxyl-potassium sulphate — is much in- 
creased, and in rare instances the urine has a blue color 
and contains a deposit of indigo. In early times, before 
the recognition of the cholera bacillus, the high indoxyl 
was considered an important element in the diagnosis 
of cholera. It should be borne in mind, however, that a 
large increase in the indoxyl is frequently found in other 
conditions than cholera, such as peritonitis, intestinal ob- 
struction, etc., so that too much reliance can not be placed 
on a high indoxyl in the diagnosis of cholera. 

During the algid stage the urine invariably contains albu- 
min. The quantity varies, but it may be large and frequently 
indicates the presence of an acute nephritis. Often the albu- 
minuria disappears with the subsidence of the algid stage. 



390 DISEASES OUTSIDE OF THE URINARY TRACT. 

The sediment contains renal casts, often in large num- 
bers, many renal cells, and a few (or numerous) blood 
globules. If an acute nephritis, the quantity of blood will 
be large, and there will be a large number of brown granu- 
lar, blood, epithelial, and fibrinous casts. 

After the third day, in a favorable case, the quantity of 
urine rapidly increases, the color is pale, and the specific 
gravity is very low. Coincident with this increase of the 
urine there is a rise in the urea, chlorides, phosphates, and 
other solids. The urine may temporarily exceed the normal 
— for example, it may rise to 60 to 80 grams and then 
gradually return to the normal. The chlorides and phos- 
phates, however, do not, as a rule, exceed the normal. In 
case of an acute nephritis during the algid stage a typical 
convalescent stage of acute nephritis is seen when the patient 
begins to improve. 

But the complication of an acute nephritis during the col- 
lapse period may be the direct cause of death by uremic 
coma. In cholera, after the third day, if the quantity of 
urine does not increase, the albumin does not diminish, and 
the urea and chlorine do not begin to rise in quantity, the 
prognosis can be considered very grave. 



SCARLET FEVER, 

The urine in this disease is subject to much variation. It 
is very common, and, indeed, the rule to find evidences in 
the urine of a severe renal congestion or an acute nephritis 
(sometimes the acute interstitial form). But in many in- 
stances the kidneys escape without greater damage than 
occurs in other acute febrile affections. An acute nephritis is 
most common in the second or third week of the disease, and 
may develop after a very mild attack of scarlet fever. Not 
infrequently, an acute nephritis makes its first appearance 
late in the period of desquamation, when it usually exists 
in a mild form. As a rule, the earlier it develops, the more 
severe it is. 

The renal disturbance varies greatly in intensity, but in 
all instances during the height of the fever the urine is 
diminished in quantity and of high specific gravity. It has 
a high or smoky color, an intensely acid reaction, and the 
normal solids are relatively increased, especially the urea 
and uric acid ; they are absohttcly diminished except during 



SCARLET FEVER. 391 

the first day or two of the disease. If there be dropsy, the 
chlorides and urea are very much reduced, especially the 
former. Three distinct grades of cases may be recognized. 

Mild Cases. — The urine has a high color, and invariably 
contains albumin — usually the slightest possible trace to a 
trace. The sediment contains an occasional (or few) hyaline, 
granular, and brown granular casts, renal cells, and a few 
blood globules, free and attached to casts ; in other words, 
there is evidence of a mild renal congestion or active hyper- 
emia. Edema is absent, and the convalescence from the 
fever is scarcely interrupted. 

Severe Cases. — The urine has a smoky color and con- 
tains considerable albumin — usually varying in amount be- 
tween a large trace and j{ of i per cent. The sediment 
contains many hyaline, granular, and brown granular, a few 
epithelial, blood, and fibrinous casts ; also many renal cells 
and frequently small caudate cells from the superficial layer 
of the pelvis of the kidney ; considerable altered blood, and 
a few pus-corpuscles — the evidences of an acute pyelo- 
nephritis. Edema, especially about the eyelids, is a con- 
stant symptom ; there may be edema of the feet. The 
renal symptoms then dominate the entire case. The con- 
dition may continue and finally become chronic, but fortu- 
nately, in a majority of the cases, the disease yields to judi- 
cious treatment, and complete recovery takes place. 

Very Severe Cases. — In this class of cases there is 
usually either complete suppression of urine or the passage 
of a small quantity of very dark (almost black) urine, 
which contains a high quantity of albumin — from ^ to 
I i^ per cent. The sediment contains the same elements 
that are found in the severe cases, but in much larger num- 
bers — a very severe acute pyelonephritis. There is marked 
dropsy, vomiting, and convulsions, and the child dies with 
the symptoms of acute uremia. 

In the favorable cases of acute pyelonephritis the third or 
convalescent stage soon makes its appearance, when the 
quantity of urine increases, the color is very slightly smoky 
or pale, and fat appears in the renal cells and is found 
attached to the casts. As previously stated, with judicious 
treatment complete recovery usually takes place. Occa- 
sionally, convalescence becomes prolonged and a chronic 
nephritis results. Sometimes a marked chronic pyelitis is 
the result of the acute pyelitis. 



392 DISEASES OUTSIDE OF THE URINARY TRACT. 

The urine in scarlet fever should in all cases be carefully 
watched, owing to the fact that renal complications are 
among the most common. 

DIPHTHERIA. 

In diphtheria, as in other acute infectious diseases, renal 
complications are common ; they are, however, less common 
than in scarlet fever. The quantity of urine is diminished ; 
the color is high, or, if an acute nephritis, smoky ; the spe- 
cific gravity is high — 1025 to 1035. Relatively, the normal 
solids are increased, but absolutely, diminished. Albu- 
minuria is a constant symptom in all severe cases, and, in 
fact, albumin is present in nearly all of the milder cases. 
It varies in amount from the slightest possible trace to a large 
trace. If an acute nephritis develops, it may exceed y^ of 
I per cent. The sediment contains renal casts, renal cells, 
and a small amount of blood both free and on casts — evi- 
dences of an active hyperemia. 

An acute nephritis is, however, not uncommon. It may 
appear quite early in the disease. Occasionally, it begins 
with complete suppression of urine. In comparison with 
scarlet fever the renal changes lead less frequently to gen- 
eral dropsy. The sediment usually contains, besides brown 
granular, blood, epithelial, and fibrinous casts, many renal 
cells, much blood, and numerous small caudate cells from 
the pelvis of the kidney — evidences of an acute pyelo- 
nephritis. The course of the nephritis is usually favorable. 
Occasionally, there are convulsions, and the patient dies from 
acute uremia. Sometimes a chronic nephritis follows an 
acute nephritis. Acute nephritis is a less frequent compli- 
cation of diphtheria since the advent of the antitoxine treat- 
ment of this disease. 

Hibbard and Morrissey^ have found that a glycosuria is 
not uncommon in diphtheria. 

SMALLPOX. 

In this disease the urine has the usual typical character- 
istics of fever. The quantity of urine is small, the coloring- 
matters are increased, and the specific gravity is high. 
Relatively and absolutely, the urea is generally increased, 
but it may, rarely, be absolutely much diminished ; under 

^ " Journ. of the Society of Med. Sciences," Feb., 1898. 



ACUTE GENERAL PERITONITIS. 393 

such circumstances, leucin and tyrosin may appear in the 
urine instead of urea. The chlorides, sulphates, and phos- 
phates are absohitcly somewhat diminished. The uric acid 
is increased, and the urine, on cooling, frequently deposits 
amorphous urates. 

Albumin is invariably present in the urine in all cases of 
smallpox, and it generally makes its appearance with the 
onset of the disease. The sediment contains renal casts, 
renal cells, and a moderate amount of blood both free and 
adherent to casts. An active hyperemia, which is usually 
quite severe, is the rule. Occasionally, a true acute 
nephritis develops, especially in the malignant forms. The 
urine frequently contains bile pigment. In the hemorrhagic 
form of the disease hemoglobinuria may be a prominent 
feature of the urine. Care should be taken not to confound 
a hemoglobinuria with a hematuria accompanying an acute 
nephritis. 

ACUTE GENERAL PERITONITIS* 

In this disease the quantity of urine is very small, the 
color is high, and the specific gravity is above the normal. 
A prominent feature of the urine is the very large excess of 
indoxyl. Relatively, the normal solids are increased, except 
the chlorides, which are very much diminished or absent ; 
absolutely, the solids are diminished. Albumin is generally 
present, and in the sediment will be found renal casts, renal 
cells, and a variable amount of blood — in other words, 
evidences of a more or less severe active hyperemia of the 
kidneys. 

In localized peritonitis the chlorides are not, as a rule, 
much diminished, if at all ; the degree of diminution is, 
however, dependent on the extent of the pathologic process 
and the amount of serous exudation. 



INTESTINAL OBSTRUCTION. 

In this condition the urine is small in amount, and there 
may be almost complete suppression, particularly when the 
obstruction is high up in the bowel. This is probably due 
to the excessive vomiting and the small amount of liquid 
taken. The urine has a high color, and the specific gravity 
is above the normal — 1025 to 1035. Relatively, the solids 
are increased ; absolutely, diminished. When the obstruc- 



394 DISEASES OUTSIDE OF THE URINARY TRACT. 

tion occurs in the small intestine, the indoxyl is usually very 
high ; in one case the amount of indoxyl reported was as 
high as 98 milligrams. Albumin is usually present, but in 
small amount ; and the sediment contains renal casts, renal 
epithelial cells, and a little blood. In the majority of cases 
of intestinal obstruction the renal disturbance is of the 
nature of a renal congestion or toxic irritation. 



ACUTE YELLOW ATROPHY OF THE LIVER» 

The twenty-four-hour quantity of urine is small, the re- 
action is strongly acid, and the specific gravity is low. The 
urine contains both bile pigments and the bile acids. Rela- 
tively and absolutely, the normal solids are much diminished. 
The urea is present in very small amount or it may be 
absent. Instead of the urea, leucin and tyrosin, one or 
both, are usually, although not constantly, present in the 
urine ; of 23 recent cases collected by Hunter, in 9 neither 
was found; in 10, both were present; in 3, tyrosin only; 
in I, leucin only. Both leucin and tyrosin have character- 
istic crystalline shapes (see pp. 227, 228), and are found in 
the urinary sediment. In the search for these crystals it is 
advisable to previously render the urine acid with acetic acid 
and concentrate by evaporation. The phosphates and uric 
acid are very much reduced. The urine always contains 
albumin, which may be present in considerable quantity — 
^ to i^ of I per cent. The sediment contains numerous 
hyaline, granular, and fatty casts, fatty renal cells, and 
compound granule cells ; in other words, the urine indicates 
a more or less marked fatty degeneration of the kidneys. 
The casts and renal cells are usually stained yellow by the 
bile pigment. 

Acute yellow atrophy is of rare occurrence and is rapidly 
fatal. It is characterized by jaundice and marked cerebral 
symptoms, and anatomically, by extensive necrosis of the 
liver-cells with reduction in the volume of the organ. The 
symptoms produced by phosphorus-poisoning closely 
simulate those of acute yellow atrophy, but it should be 
borne in mind that the two conditions are not identical. 



HYSTERIA. 395 



HYSTERIA. 

During and immediately following an attack of hysteria 
the twenty-four-hour quantity of urine is much increased, 
not infrequently going as high as 5000 c.c. The color is 
very pale and watery ; and the specific gravity is low — 1002 
to 1012 ; the reaction is faintly acid. Relatively, the solids 
are much diminished ; absolutely, normal or only slightly 
diminished, and sometimes they are increased. The urine 
is frequently free from albumin ; on the other hand, it may 
be present in very small amount — slightest possible trace. 
The sediment usually contains only a moderate excess of 
squamous epithelial cells. If the urine contains albumin, 
after centrifugalizing the sediment will be found to contain 
an occasional hyaline and finely granular cast, renal cell, 
and blood globule — in other words, evidences of a very 
slight active hyperemia, perhaps the result of increased 
activity of the kidneys. Since hysteria is more common in 
the female than in the male, the presence in the urine of a 
profuse vaginal secretion will in many instances account for 
a very slight albuminuria, without necessarily having any 
evidence of a renal disturbance. 

Charcot has called attention to the fact that in hysteria 
the quantity of urine may be very small. He records a 
case in which the patient suffered from vomiting and diar- 
rhea, and in which there was complete suppression of urine 
for eleven days. Deception was not possible, as the 
patient was closely watched. 



CEREBROSPINAL MENINGITIS. 

In this disease the urine has the characteristics of a fever 
urine accompanied by exudation. The quantity of urine is 
small ; the color is normal or pale, and sometimes it is 
high ; the specific gravity is usually somewhat above the 
normal ; and the reaction is only faintly acid or it may be 
alkaline. The total quantity of urea is high, the increase 
usually amounting to 25 per cent, or more (Purdy). The 
phosphates are much increased in the early part of the dis- 
ease, so that upon performing the heat test for albumin 
without the customary addition of acetic acid, an abundant 
precipitate is thrown down by the test ; later in the disease 
the phosphates become diminished. The chlorides are 



396 DISEASES OUTSIDE OF THE URINARY TRACT. 

greatly diminished from the first and may, in rare instances, 
be absent. Albumin, which is invariably present, varies in 
quantity from the slightest possible trace to ^ or i^ of i 
per cent., but is dependent on the amount of renal involve- 
ment and the quantity of blood present. Glycosuria has 
been noted in some instances. The sediment contains hya- 
line, granular, and brown granular casts, renal epithelial 
cells, and more or less blood. 

The renal disturbance is usually an active hyperemia, 
which may be quite severe. Rarely, an acute nephritis 
with marked hematuria develops, especially in the malig- 
nant types. 

In certain cases there is sometimes doubt as to the 
diagnosis between typhoid fever and an acute cerebrospinal 
meningitis. Aside from a bacteriologic investigation, an 
examination of the urine is sometimes of assistance in arriv- 
ing at a conclusion. The principal differences in the urine 
in the two diseases are as follows : 

Meningitis. Typhoid Fever. 

Fever Urme with Exudation. Fever Urine without Exudation. 

Color. — Normal or pale. Color. — Very high. 
Reaction. — Faintly acid, neutral, or Reaction. — Strongly acid. 

alkaline. 
Chlorine. — Much diminished or ab- Chlorine. — Slightly diminished. 

sent. 

Phosphates. — Much increased. Phosphates. — Diminished. 

MELANCHOLIA. 

In this disease the total quantity of urine is usually much 
diminished, no doubt in part due to the ingestion of very 
little liquid. The specific gravity is high, and the coloring- 
matters and normal solids are relatively increased. The 
urine is frequently heavily loaded with urates and oxalates. 
The indoxyl is generally increased. The irritating action 
of the concentrated urine, and in some instances the 
mechanic irritation by the crystals of uric acid or calcium 
oxalate, may be the cause of slight albuminuria and a renal 
congestion (active hyperemia). 

ACUTE MYELITIS. 

Owing to an involvement of the sphincters in this dis- 
ease retention or incontinence of urine is an early symptom. 
An acute or chronic cystitis may rapidly develop, when the 



EPILEPSY. 397 



urine becomes faintly acid or alkaline, bloody, and purulent. 
In such cases the danger of a pyelonephritis by extension 
is ver}'" great ; not infrequently, death occurs during uremic 
coma. One very prominent feature of the urine in acute 
myelitis is a marked increase in the indoxyl. 



EPILEPSY. 

Temporary albuminuria accompanied by more or less 
renal disturbance is of frequent occurrence, especially in 
those cases of epilepsy in which the convulsive seizures 
succeed each other very rapidly. Immediately following 
the attacks the quantity of urine is often much increased, 
the color pale, the specific gravity low, and the reaction 
faintly acid. At this time the urea, phosphates, and uric 
acid are said to be increased. 

As suggested by Taylor, ^ the question of auto-intoxica- 
tion is to be considered as a possible cause of albuminuria 
and the renal disturbances in cases of severe nervous 
affection. It is quite probable that the nervous disease 
itself may give rise to certain products that are later ex- 
creted by the kidneys. This is, however, contrary to the 
view, as generally held, that the effete products normally 
excreted by the urine are sometimes retained in the body, 
and that they are the direct cause of various nervous dis- 
turbances. 

ACUTE ARTICULAR RHEUMATISM. 

In acute rheumatism the urine has the characteristics of 
that of an acute disease. It is small in quantity, has a high 
color, and a high specific gravity — 1025 to 1030. Rela- 
tively, the quantity of urea is increased, absohitely, usually 
diminished. The uric acid is often both relatively and abso- 
lutely increased, sometimes to a much larger extent than in 
most of the other acute diseases. The urine, upon cooling, 
may contain an abundant deposit of amorphous urates. 
The chlorides and phosphates are only moderately dimin- 
ished in an uncomplicated case ; the sulphates are often in- 
creased. . If a pericarditis develops, the chlorides and phos- 
phates become very much diminished, and may temporarily 
entirely disappear from the urine. A sudden fall in the 

1 '* Boston Med. and Surg. Journ.," Sept. 22, 1898. 



398 DISEASES OUTSIDE OF THE URINARY TRACT. 

amounts of these two constituents of the urine is, therefore, 
indicative of a serious compHcation. 

Albumin is usually present, but in very small amount — 
slightest possible trace. Rarely, it occurs in large quantity 
attended by an acute nephritis, of which the urinary sedi- 
ment bears abundant evidence. In the average case of 
acute rheumatism the sediment contains only a very few 
renal casts, renal cells, and an occasional blood globule, free 
and adherent to casts ; in other words, the sediment is char- 
acteristic of an active hyperemia. 



GOUT. 

During an attack of gout the volume of urine is gener- 
ally diminished, the color is high, and the specific gravity 
is above the normal. The uric acid is diminished during 
the paroxysm ; although it is probably formed in unusual 
quantities in this disease, the deposit of urates in the joints 
and tissues accounts for the deficient elimination by the 
kidneys. Usually, the quantity of urea is not materially 
altered during the paroxysm of gout. The phosphates are 
generally much diminished. Albumin is nearly always 
present, but usually in very small amount. The sediment 
contains hyaline, granular, and brown granular casts, renal 
cells, and altered blood free and adherent to casts — the evi- 
dences of a secondary active hyperemia of the kidney. 

Between the attacks or paroxysms, the quantity of urine 
is normal or even increased. The normal solids are usually 
about normal, except the uric acid, which is now eliminated 
in increased amount ; this is especially marked immediately 
following the paroxysm. Evidence of a more or less marked 
renal irritation persists between the attacks. 

It should be borne in mind that in chronic gout a chronic 
interstitial nephritis is not uncommon. Under such circum- 
stances the quantity of urine is increased ; absolutely, the 
urea is much diminished, albumin is present, but usually in 
minute quantity, and the casts in the sediment are generally 
of the small, narrow, hyaline, and finely granular order. 

Sugar may be found intermittently in the urine of gouty 
persons — gouty glycosuria. The condition may pass into 
true diabetes, but it is usually very amenable to treatment. 
Oxaluria may also be present. Calculi are not uncom- 
mon in gouty subjects. 



ANEMIA. 399 



ANEMIA. 



In the various forms of anemia the urine presents certain 
characteristics that are common to all. The twenty-four- 
hour quantity is generally diminished — looo c.c. to 1200 
c.c. ; the color is pale ; the specific gravity is below the 
normal — about i o i 5 ; and the reaction is acid. Relatively 
and absohitely the normal solids are diminished, but the 
degree of diminution is dependent largely on the appetite 
and general metabolism. 

In simple aneuiia and chlorosis the urine occasionally 
contains the slightest possible trace of albumin and formed 
renal elements in the sediment ; on the other hand, albu- 
min and renal casts may be absent. 

In leukemia the presence of a minute trace of albumin 
and renal casts is perhaps more common than in simple 
anemia. Fatty cells and fat adherent to the casts are not 
uncommon. The indoxyl is frequently increased. Abso- 
lutely, the urea is diminished. The uric acid excreted is 
always in excess, and, perhaps, as suggested by Salkowski, 
stands in direct relation to the splenic tumor or to the 
abundant leucocytes. The proportion of uric acid to urea 
may be as high as i to 15. 

In pernicious aneinia the urine, although usually pale, 
may be highly colored from the excess of so-called patho- 
logic urobilin (Hunter and Mott). The uric acid is in- 
creased. Albumin, varying in quantity from the slightest 
possible trace to a trace, is usually present in the late stages 
of the disease, and the sediment usually contains renal casts, 
granular renal cells, and a small quantity of blood. Von 
Jaksch has noted the presence of peptonuria in this disease, 
but so far as known it has little or no significance. 

SCURVY. 

In. this disease the quantity of urine is reduced, the 
coloring-matters are increased, and the urine may contain 
a large amount of blood pigment — hemoglobinuria. Abso- 
lutely, the normal solids are diminished, especially the 
chlorine. The urine is generally albuminous, and some- 
times albumin is present in large amount, especially if there 
be hemoglobinuria or an acute nephritis. The sediment 
usually contains renal casts, renal cells, and in case of 



400 DISEASES OUTSIDE OF THE URINARY TRACT. 

hemoglobinuria an abundance of brown granular matter. 
Hematuria is sometimes present, and under all circum- 
stances should be distinguished from a hemoglobinuria. 
The author has occasionally met with a genuine acute 
nephritis in this disease. A more or less marked renal 
congestion is not uncommon. 

CARBOLIC ACID POISONING. 

In this condition the urine is diminished in quantity ; 
the color is variable, being usually pale or normal when 
freshly voided, but upon standing exposed to the air 
becomes smoky and finally very dark ; occasionally, the 
urine is dark when it is passed. This characteristic change 
of color, following the external or internal use of carbolic 
acid and other phenol compounds, is due to an oxidation 
of the decomposition products of the phenol or phenol 
compounds. (See Color of the Urine, p. 25.) The 
specific gravity is usually normal or diminished ; it may be 
above the normal. The reaction is acid. Relatively, the 
normal solids are normal or diminished, depending upon 
the severity, and occasionally they are relatively increased ; 
absolutely, diminished, especially the ordinary sulphates, 
while the conjugate sulphates are much increased. (See 
Phenol-potassium Sulphate, p. 89.) 

The urine contains albumin ; usually a very slight trace, 
but in the severe cases it may be as high as ^ of i per 
cent. The sediment contains hyaline, granular, and brown 
granular, and sometimes epithelial casts, renal cells, and 
abnormal blood free and adherent to the casts. A more 
or less marked renal congestion is the rule, but occasion- 
ally a true acute nephritis is present. 

Care should be taken not to confound a dark urine fol- 
lowing the use of phenol compounds with a urine contain- 
ing melanin, in which case the urine is often pale when 
passed, but upon exposure to the air becomes dark. (See 
Melanin, p. 194.) 

POISONING BY PHOSPHORUS AND ARSENIURETED 
HYDROGEN. 

The characteristics of the urine in cases of poisoning by 
arseniureted hydrogen and phosphorus are, for the most 
part, identical. Hemoglobinuria is the principal symptom. 



POISONING BY PHOSPHORUS. 401 

The quantity of urine is diminished. The normal solids are 
greatly diminished, especially the urea. In severe cases 
leucin and tyrosin may appear in the urine. Albuminuria is 
invariably present ; usually, the amount of albumin is large, 
although the quantity will depend on the severity of the 
case. The sediment will contain numerous brown granular 
and fatty casts, fatty and brown granular renal and com- 
pound granule cells, a variable but usually small amount of 
blood, and sometimes crystals of leucin and tyrosin — evi- 
dences of extensive fatty degenerative changes in the 
kidney phis a hemoglobinuria. 

26 



APPENDIX A. 



METHOD OF RECORDING URINARY EXAMINA- 
TIONS* 

The advisability of making and preserving urinary records 
is obvious, since it is only by this means that the progress 
of disturbances or diseases of the kidney (favorable or un- 
favorable) can be followed from week to week, or month to 
month, or year to year. Such records should be made on 
separate sheets of paper provided for the purpose and in- 
corporated with the clinical histor}^ and physical examina- 
tion of the patient, or be kept in a book by themselves with 
cross-references to the volume containing the clinical his- 
tory, etc. For ordinar}^ use printed urine blanks (see p. 
403) can be obtained, and as each test is made the result, 
indicated by abbreviations, should be affixed to the spaces 
left for the purpose. 

The abbreviations used upon the blank forms have the 
following meanings : Upli. = urophaeine ; Ind. = indoxyl ; 

+ - . . 

CI. = chlorine ; U. = urea ; U. = uric acid ; Sf. = sul- 
phates ; £, P. = earthy phosphates ; A. P. = alkaline 
phosphates ; Sp. Gr. = specific gravit>^ ; Sed. = sediment ; 
A/d. = albumin, etc. 

The common abbreviations used in recording the results 
of analysis are : -p = increased ; — = diminished ; n = 
normal. For much increased or much diminished : m -r- 
and m — , respectively ; similarly, si. -f and si. — for a 
slight increase and slight decrease. Other abbreviations, 
according to the habit and convenience of the recorder, 
may equally well be adopted. 

The plan of incorporating the urinary records into book 
form is to be encouraged, especially for those who make a 
large number of analyses. Such a book properly indexed 
can be prepared by any competent printer at a moderate 
cost. A record of this kind is far more serviceable and 
convenient than the separate sheets. 

402 



RECORD OF URINARY EXAMINATIONS. 403 



ANALYSIS OF URINE. 



Date 

Name. 

Amt. in twe7ify-fotir ho2c?'s = Sp. Gr. = 

Color = Sed. = 

Odor = 
Reaction = 

Uph. = 17. (fo) = a. == E. P. 

Ind. = C/.= S/.= A. P. 

Albumin = 
Bile Pigments = 
Sugar = 
Sediment = 



U. = grams. P^O^=^ 

Quant. 



a. = *' Sugars 

Diagnosis = 



404 URINARY EXAMINATIONS. 



Tabular Atrangfement of Helle/s Tests (modified). 

Physical Properties. 
Color. — Pale, normal, high, or dark. 
Odor. — 

Reaction. — Acid, neutral, or alkaline. 
Sp. Gr. — By urinometer. 
Sediment. — Slight, considerable, or much. 

Normal Constituents. 

TjROPHiEiNE (Uph.). — 7 c.c. HgSO^ + double quantity of Ur. 
= immediate garnet-red color. 

INDOXYL (Ind.).— 15 c.c. HCl (+ 2 gtt. HNO3) -f 30 gtt. 
Ur. = amethyst color, developing in from five to twenty 
minutes. 

Urea (U.). — With NaOBr. (Squibb's apparatus.) 

Uric Acid (U.). — >^ tt. Ur. + HCl = U cryst. in 24 hours. 

Chlorine (CI.).— Ur. -f HNO3 + AgNOg (1:8) = solid 
ball of AgCl, if normal. 

Sulphates (Sf.).— i^ tt. Ur. + BaCl^ sol. (1:4 sol. + HCl) 
= ppt. y2 concavity of tt. in from eighteen to twenty- 
four hours, if normal. 

Earthy Phosphates (E. P.). — }4 tt. Ur. + NHpH = ppt. 
i^ to ^ in. in tt., in from eighteen to twenty-four hours, 
if normal. 

Alkaline Phosphates (A. P.). — Filtrate from E. P. + MgSO^ 
sol. (MgSO, + NH^Cl -f NHpH) = ppt. >^ to ^ in. 
in tt., in from eighteen to twenty-four hours, if normal. 



Abnormal Constituents. 

Albumin (Alb.). — Heat or HNO^ = coagulum or zone. 

Bile Pigments. — Marechalt's test (iodine). 

Sugar. — Fehling's solution. Phenylhydrazin test. Fermenta- 
tion test. 

Sediment. — Let settle or centrifugalize, and examine by micro- 
scope. 



ORDER OF APPLYING TESTS. 405 



ORDER OF APPLYING TESTS. 

In the routine analysis of a urine it is advisable first to 
note the twenty-four-hour quantity, the color, the odor if 
at all peculiar, the reaction, and the specific gravity. The 
next in order should be the tests for urophaeine and indoxyl, 
and then the test for albumin. If more than a trace of 
albumin be present, it must be removed before testing for 
chlorides, sulphates, or sugar. Having removed the albu- 
min by heat from one-third or one-half of a test-tube of the 
urine after the addition of one drop of acetic acid (see p. 
131) the test for chlorides, sulphates, and sugar should 
then be performed. If in the test for albumin a zone of 
acid urates appears, it should be noted. Such a zone 
indicates a relative excess of uric acid and urates. The 
tests for earthy and alkaline phosphates are next in order, 
and then the test for bile pigments. 

The quantitative test for urea should be performed in 
every instance, and this is most conveniently done by 
means of the Squibb or the Doremus apparatus. The per- 
centage should be noted, and the total number of grams of 
urea calculated. If sugar be present, it should also always 
be quantitated, and the total quantity reported in grams. 

The amount of sediment that a urine contains can only 
be determined after the urine has completely settled. The 
degree of opacity of the urine can not always be considered 
a criterion of the amount of sediment present. A urine may 
be very turbid, for example, by bacteria, and yet contain 
very little sediment. As soon as the sediment has com- 
pletely settled, it should be carefully examined by means 
of the microscope for casts, renal cells, fatty cells, fat adher- 
rent to the casts, blood, pus, crystalline elements, etc. 

METHOD OF MAKING DIAGNOSES OF DISEASES OF THE 
KIDNEYS FROM THE URINE, 

The diagnoses of the different diseases of the kidneys 
are made chiefly by exclusion. 

It has been shown that, even in a single affection of the 
kidneys, the characteristics of the urine vary with the severity 
of the process and the extent of the diseased condition ; 
furthermore, that diseases of the kidneys are very liable to 
become complicated by other pathologic conditions of these 



406 APPENDIX A. 

organs. Thus, the urine becomes modified to a greater or 
less extent from what one would find if the original disease 
were uncomplicated. For example, a subacute or chronic 
disease of the kidneys is very liable to be complicated by a 
more or less severe acute process ; under such circum- 
stances, the underlying subacute or chronic process may be 
partially or entirely obscured by the acute complication. 
Obviously, an absolute standard of disease, to which an un- 
known specimen of urine shoidd conform, is entirely out of the 
question. In other words, a urinary disease is not invariably 
accompanied by a urine of specific character, but by charac- 
teristics subject to more or less variation. 

In the foregoing pages of this work the author has 
endeavored to outline a fairly typical urine of each disease. 
Having made an accurate examination of an unknown speci- 
men of urine, it will be found that the characteristics of such 
a urine harmonize in a general way with those known to be 
associated with this or that disease. 

In the consideration of a given urine that shows evidence 
of a renal disturbance or disease (presence of renal casts) 
the first and most important feature from the standpoint of 
diagnosis is the total quantity of urine. 

A diminished quantity (less than 1500 c.c.) is, as a rule^ 
indicative of any of the following conditions : 

1. Active hyperemia. 

2. Passive hyperemia. 

3. Acute nephritis (first and second stages). 

4. Subacute glomerular nephritis (all stages). 

5. Chronic renal diseases toward death. 

An increased quantity (more than 1500 c.c.) is strongly 
suggestive of any of the following conditions : 

(a) Convalescence from severe active hyperemia. 

(^) Convalescence from acute nephritis. 

{c) Chronic interstitial nephritis. 

(^) Chronic diffuse nephritis. 

(£') Amyloid infiltration. 

Having limited the probable renal disturbance or disease 
to the class characterized by a small or a large quantity of 
urine, the next step is to distinguish between the different 
renal conditions of that class by means of the quantities of 
normal solids, the amount of albumin, and the peculiarities 
of the sediment — i. e., the presence or absence of blood on 
casts, the presence or absence of fat from the kidney, the 



METHOD OF MAKING DIAGNOSES. 407 

size and character of the renal casts, etc. In this way the 
most probable disturbance or disease of the kidneys can 
usually be narrowed down to one or, perhaps, two of the 
conditions under consideration. 

Having arrived at the most probable renal affection, the 
next step is to determine the location and nature of any 
complications that may be present, whether in the kidneys 
or in some other portion of the urinary tract. 

In the application of this plan of urinary diagnosis it is 
obvious that the student must thoroughly familiarize him- 
self with the characteristics of the urine of each disease of 
the kidneys, as well as of those of other portions of the 
urinary tract. 



APPENDIX B. 



REAGENTS AND APPARATUS FOR QUALI= 

TATIVE AND QUANTITATIVE 

ANALYSIS OF URINK 

The reagent bottles should be made of pure, clear glass, 
free from lead and other impurities. Those for liquid 
reagents should have a capacity of about 250 c.c, while 
those for solid reagents need not have a capacity over 
120 c.c. All bottles should be fitted with ground-glass 
stoppers, and should have labels upon them in raised glass 
letters, or a ground-glass label with black letters, and the 
chemic symbol of the reagent below and separate from the 
lettering. 

Many of the reagents given below are not really neces- 
sary for the ordinary routine analysis of urine, but for 
efficient laboratory work all of those given will be found 
necessary. 

LIQUID REAGENTS. 

Sulphuric acid, C. P. (H2- Tinct. iodine, U. S. P. 

SOJ. Sol. lead acetate (1:5). 

Hydrochloric acid, C. P. Sol. basic lead acetate (i : 5). 

(HCl). Alcohol, 95 per cent. 

Nitric acid, C. P. (HNO3). Sodic hydrate for urea. (See 
Acetic acid (HC2H3O2). p. 52.) 

Ammonic hydrate (NH^- Bromine (modified) for urea. 

OH). (See p. 52.) 

Sodic hydrate (NaOH), U. Fehling's solution. (Seep. 

S. P. I49-) 

Magnesia mixture. (See p. A. Cupric sulphate so- 

109.) lution. 

Sol. potassium ferrocyanide B. Alkaline tartrate so- 

(i : 10). lution. 

408 



REAGENTS. 



409 



Sol. barium chloride 
p. 113.) 



Sol. ferric chloride- 

(I : 10). 
Millon's reagent. 

170.) 
Esbach's reagent. 

I33-) 
Sol. silver nitrate (1 



(See 
-aqueous 

(See p. 

(See p. 
:8). 



Phenylhydrazin (pure). 

Chloroform. 

Formaline. 

Sol. boric acid (saturated). 

Standard sol. silver nitrate. 
(See p. 103.) 

Standard sol. uranium ni- 
trate. (See p. no.) 

Distilled water. 



SOLID REAGENTS. 

[All reagejits should be chemically pure. ) 



Cupric sulphate. 
Caustic soda. 
Sodium chloride. 
Potassium iodide. 
Potassium chromate. 
Ammonium sulphate. 
Magnesium sulphate. 
Ammonium chloride. 
Sodium acetate. 
Potassium ferrocyanide. 



Potassium chlorate. 
Picric acid. 
Citric acid. 
Lead acetate. 
Sulphanilic acid. 
Sodium nitrite. 
Sodium carbonate. 
Mercuric chloride. 
Potassium bromide. 
Sodium nitroprusside. 



APPARATUS. 

Test-tubes. 

Test-tube brush. 

Test-tube rack. 

Bunsen burner with two feet rubber tubing, or a spirit lamp. 

Urinometer (Squibb or other of reliable make). 

Urinometer glass with foot and parallel sides. (See Fig. 2.) 

Wine-glasses. (See Fig. 13.) 

Urea apparatus (preferably Squibb' s). 

Urine glasses. (See Fig. 24.) 

Funnels, large and small. 

Filter papers (cut) 4, 6, and 8 inches in diameter. 

Glass tubing for pipettes. 

Glass rods (assorted sizes). 

Litmus paper (red and blue). 

Graduates (100, 500, and 1000 c.c). 

Evaporating dishes (assorted sizes up to one liter). 

Crucibles. 

Porcelain spatula. 



410 APPENDIX B. 

Platinum wire inserted in glass rod. 

Platinum foil. 

Burettes (50 c.c, graduated in tenths of a cubic centimeter). 

Retort stand with burette clamp attached. 

Tripod with copper-wire gauze to cover. 

Triangles. 

\\^ater-bath (preferably copper with rings). 

Crucible tongs. 

Beakers (nests of six). 

Wash bottle (500 c.c). 

Flask (250 c.c). 

Liter flask (graduated on neck). 

Graduated pipettes (5, 10, and 50 c.c). 

Dropping bottle, bulb stopper. 

Esbach's albuminometer. 

Accurate thermometer. 

Accurate balances, turning at I milligram. 

IMicroscope — Zeiss, Leitz, or Bausch and Lomb, with nose- 
piece ; objectives corresponding to 3, 5, and 7 of Leitz 
make, and i and 3 eye-pieces, Leitz make ; Abbey con- 
denser ; and -^ oil immersion lens. 

Glass sKdes, cover-glasses, cedar oil, and Canada balsam 
(in solution). 

Centrifuge capable of 2000 revolutions per minute. 



Plate io 




Jl a' fi' 



1 1 ^a 


■ 


■1 


1 






1 11 II 


■ 


■1 









r 



n 




Spectra (after Neubauer and Vogel). 

1. a, Oxyhemoglobin ; b, hemoglobin, free from oxygen. 

2. Methemoglobin : a, in neutral solution ; b^ in alkaline solution. 

3. a, Hematin in acid alcoholic solution ; 5, in ammoniacal solution ; c, 
reduced hematin. 

4. a. Urobilin in acid solution ; b, zinc salt in ammoniacal solution. 



Spectra, Continued (after Neubauer and Vogel). 

5. Hematoporphyrin : a, acid; b, alkaline; c, neutral; d, metallic 
spectra. 

6. Bilicyanin : a, in acid solution ; b, in alkaline solution. 

7. Uroerythrin. 



Plate 




^ J3 




iiiiiiiii! 




^ /i 




E b 



10 



SO 90 



130 no 



iO 30 20 10 600 589 80 70 60 50 Ifi 30 20 10 500 

I) El) 

589.3 527 517. 



J,90 SO 

F 



NDEX 



Abnormal blood, 233 

constituents of the urine, 1 19 
Abscess of the kidney, 328 

of the prostate, 355 
Absolute solids, 37 
Acetone in the urine, 173 

clinical significance of, 174 
detection of, 175 
Legal' s test for, 175 
quantitative estimation of, 175 
Acetonuria, 174 
Acid, carbonic, 1 16 

conjugate sulphuric, II5 

damaluric, 30 

damolic, 30 

fatty, 98 

fermentation, 32 

hippuric, 81 

lactic, 98 

nucleic, 76 

oxalic, 97 

phenylic, 30 

phosphoric, determination of, lio 

sarcolactic, 98 

succinic, 98 

sulphuric, 112 

taurylic, 30 
Acidity, causes of diminished, 33 

of increased, 34 
Acids, biliary, 182 
Active hyperemia, 284 

severe, 288 
Acute articular rheumatism, urine in, 

.397 
diffuse nephritis, 294 
general peritonitis, urine in, 393 
myelitis, urine in, 396 
yellow atrophy of the liver, urine 

in, 394 
Albumin in the urine, 120 

approximate estimation of, 125 

detection of, 124 

quantitative estimation of, 132 

removal of, 1 31 

testing for, method of, 124 
Albuminometer, Esbach's, 133 
Albuminuria, causes of, 121 
clinical importance of, 121 



Albuminuria, false, 123 

functional or physiologic, 122 

of adolescence, 123 
Albumoses, 1 36 

clinical significance of, 137 

detection of, 138 
Albumosuria, 137 
Alkaline carbonates, 29, 32 

phosphates, 108 
detection of, 109 

tide, 32 
Alkalinity of the urine, 32 
Alkapton, 28 

as a reducing agent, 152 
Allantoin, 77 

detection of, 78 
Almen's tannin solution, I44 
Ammoniacal decomposition of the 

urine, 33 
Ammonio-magnesium phosphate, 217 
Ammonium urate, 213 
Amorphous urates, 214 

treatment of sediment contain- 
ing, 214 
Amphoteric reaction, 33 
Amyloid concretions, 262 

infiltration, 319 
Analysis of calculi, 282 
Anemia, urine in, 399 
Antialbumose, 136 
Antipeptone, 139 
Anuria, 25 

Apparatus for analysis of urine, 408 
Appendix, 402 
Aromatic oxyacids, S^ 

substances in the urine, 8 1 
Arsenic in the urine, 188 

tests for, 189 
Ascarides in the urine, 271 



Bacillus of typhoid in the urine, 

268, 383 
Bacteria in the urine, 265 
cause of turbidity, 30 
Bacterial casts, 258 
Barfoed's reagent, 167 



411 



412 



INDEX. 



Barium chloride, standard solution of, 
114 
solution for sulphates, 1 13 
Bausch & Lomb hand centrifuge, 205 
Bile in the urine, 179 
Biliary acids, 182 

clinical significance of, 183 
detection of, 184 
isolation of, 183 
quantitative estimation of, 185 
pigments, 179 

clinical significance of, 180 
detection of, 181 
Bilirubin-calcium, 180 
Bilirubin in the urine, 226 
Biuret reaction, 141 
Black urine, 28 
Bladder, cancer of, 350 
epithelium from, 247 
inflammation of, 344 
tuberculosis of, 348 
tumors of, 350 
Blood, abnormal, 233 
in the urine, 232 

treatment of sediment containing, 

233 
normal, 232 
Blood-casts, 256 
Blood-pigment, Teichmann's test for, 

237 
Bloody color of the urine, 28 
Blue color of the urine, 28 
Boric acid as a preservative, 23 
Bowman, theory of, 17 
Bromides in the urine, 19 1 



Cadaverin, 224 
Calcium carbonate calculi, 280 
oxalate, 97, 219 
calculi, 279 

clinical significance of, 222 
crystals of, 220 
phosphate, 217 
urate, 214 
Calculi, urinary, 272 

chemic examination of, 282 
constituents of, 274 
Calculous pyelitis, 337 
Calculus, vesical, 346 
Cancer of the bladder, 350 
of the kidney, 330 
of the prostate, 359 
Cane-sugar in the urine, 172 
Carbohydrates in the urine, I47 
Carbolic-acid poisoning, urine in, 400 
Carbonates in the urine, 1 16 

alkaline, 29 
Casts, bacterial, 258 



Casts, bacterial, classification of, 250 

crystalline, 258 
epithelial, 255 
false, 259 
fatty, 257 
fibrinous, 252 
granular, 254 
hyaline, 250 
renal, 249 
waxy, 253 
Cells, compound granule, 248 

seminal, 247 
Centrifugal method of estimating al- 
bumin, 134 
chlorides, 106 
phosphates, 112 
uric acid, 71 
of obtaining sediment, 202 
Centrifuges, 204, 205 
Cerebrospinal meningitis, urine in, 

395 
Chloral in the urine, 190 
Chlorides, 100 

clinical significance of, loi 

detection of, 102 

quantitative estimation of, 102 
Chlorinated lime, solution of, 52 
Cholera, urine in, 389 
Cholesterin in the urine, 230 

detection of, 231 
Chronic diffuse nephritis, 316 

interstitial nephritis, 307 
Chyle in the urine, 30, 362 
Chyluria, 362 

Cochineal tincture as indicator, III 
Colic, renal, 327, 342, 344 
Collection of urine for analysis, 22 
Coloring matters, 91 
Color of the urine, 25 

under normal conditions, 25 

under pathologic conditions, 26 
Compound granule cells, 248 
Concretions, 272 

amyloid, 262 

calcium carbonate, 280 
oxalate, 279 

cystin, 280 

fibrin and blood, 282 

indigo, 281 

phosphatic, 279 

prostatic, 282 

uric acid and urates, 278 

urostealith, 281 

xanthin, 280 
Constituents of normal urine, 21 

of urinary calculi, 274 
Convalescence from acute nephritis, 
288 

from severe active hyperemia, 289 



INDEX. 



413 



Corpora amylacea, 261 
Cover-glasses, 208 
Cr\oscopy, urinary, 118 
Crystalline casts, 258 
Cyclic albuminuria, 123 
Cystic disease of the kidney, 331 
Cystin, 31, 223 

calculi, 280 

detection of, 225 
Cystinuria, causes of, 224 

clinical significance of, 225 
Cystitis, acute, 344 

chronic, 346 

Dark color of the urine, 27 
Day- and night-urine, 23 

collection of, 23 
Deutero-albumose, 137 
Dextrose in urine, 147. See Glucose. 
Diabetes mellitus, 370 

insipidus, 377 

phosphatic, 109 
Diabetic coma, 375 
Diacetic acid in the urine, 176 

clinical significance of, 177 
detection of, 177 
Diaceturia, 177 
Diagnosis of kidney disease, from the 

urine, 405 
Diamines in the urine, 224 
Diazo reaction, Ehrlich's, 186 
Diffuse nephritis, acute, 294 

chronic, 316 
Diminished acidity, causes of, 2i2> 

quantity of urine, causes of, 24 
Diphtheria, urine in, 392 
Distoma hematobium, 269 
Donne's test for pus, 241 
Dysalbumose, 157 

Earthy phosphates, 107 

cause of turbid urine, 29 
detection of, 109 
quantitative estimation of, III 

Echinococci, 270 

Eclampsia, puerperal, 293, 369 

Ehrlich's diazo reaction, 186 

Einhorn's saccharimeter, 162 

Electric centrifuge, 204 

Epilepsy, urine in, 397 

Epithelial casts, 255 

Epithelium in urine, 243 

Erysipelas, urine in, 388 

Esbach's albuminometer, 133 

method of quantitating albumin, 

133 
Ethereal sulphates, 84, 1 15 
formation of, 84 



Eustrongylus gigas, 271 
Extraneous substances in urine, 263 

False albuminuria, 123 

casts, 259 
Fatty acids in urine, 98 

casts, 257 
Febrile acetonuria, 174 
Fehling's solution, 149 

test for sugar, 149, 157 
Fermentation, acid, 32 

-test for sugar, 154, 161 
Ferments in the urine, 98 
Fever urine^, 380 
Fibrin in the urine, 145 

clinical significance of, I45 
detection of, 145 
Fibrinous casts, 252 
Filaria sanguinis hominis, 269, 362 
Florence reaction for seminal fluid, 

261 
Folin's method for estimating uric 

acid, 71 
Formalin as a preservative, 23 
Frohn's reagent, 155 
Functional albuminuria, 122 
Functions of the kidneys, 17 
Furfurol reaction for bile acids, 185 
for tyrosin, 229 

Garrod's method of detecting hem- 
atoporphyrin in the urine, 194 

Gases in the urine, 366 

General diseases, urine in, 381 

Globulin in the urine, 135 

clinical significance of, 135 
quantitative estimation of, 136 

Globulose, 136 

Glomerular nephritis, subacute, 302 

Glucose in the urine, 147 
bismuth test for, 155 
detection of, 148 
Fehling's test for, 149 
fermentation test for, 154 
isolation of, 148 
methylene-blue test for, 156 
Nylander's test for, 156 
phenylhydrazin test for, 152 
quantitative determination of, 157 
Trommer's test for, 149 

Glycosuria, 370 

permanent, 370, See Diabetes 

Mellitus. 
temporary, 370 
traumatic, 371 

Glycuronic acid in the urine, 1 71 

isolation and detection of, 172 

Gmelin's test for bile pigment, 181 



414 



INDEX. 



Gonococci, 268 

Gonorrhea, 360 

Gout, urine in, 398 

Gram's method of staining gonococci, 

268 
Granular casts, 254 
Grape-sugar in the urine, 147. See 

Glucose. 
Greenish sediment, 242, 328 

tint to the urine, 28 
Guanin in the urine, 72 



Halliburton's table of colors, 28 
Hand centrifuge, 205 
Heat-test for albumin, 137 
Heidenhain, experiments of, 18 
Heintze's method of estimating uric 

acid, 67 
Hematogenous icterus, 182 
Hematoidin in the urine, 226 
Hematoporphyrin in the urine, 19 1 

clinical significance of, 193 

detection of, 194 

separation of, 193 

spectra of, 192 
Hematuria, 234 

clinical significance of, 234 
Hemialbumose, 136 
Hemin crystals, 238 
Hemipeptone, 139 
Hemoglobin in the urine, 144 

oxy-, 144 

reduced, 144 
Hemoglobinuria, 364 
Hepatogenous icterus, 182 
Heteroalbumose, 137 
Heteroxanthin, 74 
detection of, 75 
High color of the urine, 25, 26 
Hippuric acid, 81 

detection of, 82 

quantitative estimation of, 83 
Hoffman's test for tyrosin, 228 
Hopkin's method of estimating uric 

acid, 68 
Hoppe-Seyler, classification of, 21 
Hyaline casts, 250 
Hydatid cysts of the kidney, 270 
Hydrochinone in the urine, 27 
Hydrogen peroxide in the urine, 1 17 
Hydronephrosis, 339 
symptoms of, 340 
urine in, 340 
Hydroparacumaric acid in the urine, 

Hydruria, 25 
Hyperemia, active, 284 
passive, 291 



Hyperemia, severe active, 288 
Hydrobromite method of quantitating 

urea, 50 
Hypochlorite method of quantitating 

urea, 50 
Hypoxanthin, 75 

detection of, 76 
Hysteria, urine in, 395 

Icterus, hematogenous, 180, 182 

hepatogenous, 180, 182 
Increased acidity of urine, causes of, 34 

quantity of urine, causes of, 24 
Indigo-blue, 85 
Indigo calculi, 281 
Indigo-red, 85 
Indoxyi-potassium sulphate, 85 

clinical significance of, 86 

detection of, 87 
Infiltration, amyloid, 319 
Inorganic constituents of the urine, 

100 
Inosite in urine, 169 

detection of, 170 

isolation of, 1 70 
Interstitial nephritis, chronic, 307 

senile, 315 
Intesdnal obstruction, urine in, 393 
Iodides in the urine, 191 
Iodoform test for acetone, 175. See 

Lieben' s Test. 
Iron in the urine, 117 

detection of, 117 

Jaffe's urobilin, 91 

Jaundice, 180, 182. See Icterus. 

Kidney, abscess of, 328 
cystic disease of, 331 
disturbances and diseases of, 284 
tuberculosis of, 323 
tumors of, 330 

Kidneys, functions of, 17 

Kjeldahl's total nitrogen determina- 
tion of urea, 58 

Kreatin, 78 

Kreatinin, 78 
detection of, 80 

Kreatinin-zinc chloride, 79 

Lactic acid in the urine, 98 
Lactose in the urine, 166 

detection of, 167 

isolation of, 166 
Laiose in the urine, 168 

detection of, 169 
Lead in the urine, 188 



INDEX. 



415 



Lead, test for, 189 
Legal' s test for acetone, 175 
Leo's sugar, 168. See Laiose. 
Leucin, 226 

detection of, 227 

Sherer's test for, 227 
Leucocytes in the urine, 238 
Leucomaines in the urine, 197 
Levulose in the urine, 167 

detection of, 168 
Lieben's test for acetone, 175 
Liebig' s method of estimating urea, 47 
Lipaciduria, 98 
Liver, acute yellow atrophy of, urine 

in, 394 
Local caseating tuberculosis, 323 
Loeffler's methylene-blue solution, 

268 
Ludwig, theory of, 18 



Magnesia mixture, 109 
Magnus-Levy method of isolating 
oxybutyric acid, /i- , from urine, 179 
Malarial fever, urine in, 387 
Marechalt's test for bile pigments, 181 
Melancholia, urine in, 396 
Melanin in the urine, 26, 194 

clinical significance of, 195 

detection of, 195 
Melanogen, 194 
Meningitis, cerebrospinal, urine in, 

395 
Mercuric nitrate, standard solution of, 

48 
Mercury in the urine, 190 

test for, 190 
Methemoglobin, 27 
Method of taking specific gravity, 37 

of testing for albumin, 124 
Methylene-blue test for sugar, 156 
Micrococcus ureae, 266 
Micro-organisms in the urine, 265 
Microscopes, 208 
Microscopic examination of urinary 

sediments, 208 
Miliary tuberculosis, acute, 323 
Milk sugar in the urine, 166 
Millon's reaction for proteids, II9 

reagent, 170 
Mohr's method of estimating chlorine, 

102 
Morner-Sjoqvist method for determin- 
ing urea, 58 
Mounting of urinary sediments, 264 
Mucin in the urine, 99, 142 
Murexide test for uric acid, 66 
Myelitis, acute, urine in, 396 



Neisser, gonococcus of, 268, 360 
Nephritis, acute diffuse, 294 

chronic diffuse, 316 
interstitial, 307 

interstitial, 307 
senile, 302 

subacute glomerular, 302 
Neubauer-Salkowski method of esti- 
mating chlorine, 104 
Nitric acid test for albumin, 124 
Nomenclature, 19 
Nonorganized sediments, 2lo 
Nonpathogenic bacteria in the urine, 

265 
Normal blood, 232 

urine, constituents of, 21 

quantitative composition of, 21 

urobilin, 91 
Nucleic acid, 76 

detection of, 77 
Nucleo-albumin, 142 

clinical significance of, I43 

detection of, 143 
Nylander's test for sugar, 156 

Obstruction, intestinal, urine in, 

393 
Obstructive suppression, 25 
Odor of the urine, 30 
Oliguria, 25 
Order of application of chemical tests, 

405 
Organic constituents of normal urine, 

41 
Organized sediments, 232 
Origin of urobilin, 91 
Oxalate of calcium, 97, 219 

crystals of, 220 
Oxalic acid in the urine, 97 
Oxyacids, aromatic, 83 
Oxybutyric acid, ^-, in the urine, 162, 
178, 377 
clinical significance of, 178 
isolation of, 179 
Oxyhemoglobin, 144 

Par AOXYPH EN YL- ACETIC acid in the 

urine, 83 
Parasites, 269 
Paraxanthin, 76 

detection of, 76 
Parkes' table of urinary constituents, 

21 
Passive hyperemia, 291 
of pregnancy, 292 
Pathogenic bacteria in the urine, 267 
Pathologic urobilin, 91 
Peculiar odor of the urine, 31 



416 



INDEX. 



Pelvic epithelium, 245 
Penicillium glaucum, 267 
Pentoses in the urine, 173 

detection of, 173 
Pepsin in the urine, 98 
Peptone, 139 

clinical significance of, 139 

detection of, 140 

separation of, 140 
Peritonitis, urine in, 393 
Permanent glycosuria, 370. See Dia- 
betes Mellitus. 
Pettenkofer' s test for bile acids, 184 
Phenol-potassium sulphate, 89 
clinical significance of, 89 
detection of, 90 
determination of, 90 
Phenylglucosazone, 153 
Phenylhydrazine test for sugar, 152 
Phosphates, 107, 216 

alkaline, 108 

clinical significance of, 108, 218 

earthy, 107 

quantitative determination of, lio 

separate estimation of earthy and 
alkaline, iii 
Phosphatic diabetes, 109 
Phosphaturia, 108 
Phosphorus-poisoning, urine in, 400 
Physical properties of the urine, 24 
Physiologic albuminuria, 122 
Pigments, biliary, 179 
Piotrowski's reaction forproteids, II9 
Pipette for sediments, 207 
Piria's test for tyrosin, 229 
Pneumaturia, 366 
Pneumonia, urine in, 385 
Polariscope, estimation of sugar by, 

162 
Polyuria, 25 

Potassium ferrocyanide test for albu- 
min, 128 

permanganate, standard solution of, 
69 

urate, 214 
Preservation of urinary sediments, 263 
Preservatives for urine, 23 
Prostate, abscess of, 355 

cancer of, 359 
Prostatic epithelium, 247 

plugs, 259 
Prostatitis, acute, 353 

chronic, 355 

tubercular, 358 
Protalbumose, 137 
Proteids in the urine, 119 
color-reactions of, 1 19 
general precipitants of, 1 20 
reactions of, 1 19 



Proteids in the urine, separation and 

identification- of, 141 
Proteoses, 136 
Ptomaines in the urine, 196 
Puerperal eclampsia, 293, 369 
Pulmonary tuberculosis, urine in, 386 
Purdy's electric centrifuge, 204 

method of quantitating sugar, 160 
Pus in the urine, 238 

clinical significance of, 241 
Donne's test for, 241 
Pus-casts, 257 
Putrescin, 224 
Pyelitis, acute, 333 

calculous, 337 

chronic, 335 
Pyonephrosis, 341 

symptoms of, 342 

urine in, 342 
Pyuria, 238 

Quantitative composition of the 

urine, 21 
determination of albumin, 1 32 

of bile acids, 185 

of chlorides, 102 

of globulin, 136 

of hippuric acid, 83 

of phosphates, no 

of sugar, 157 

of sulphates, 1 13 

of urea, 47 

of uric acid, 67 
Quality of urine in twenty-four 
hours, 24 



Reaction of the urine, 31 
Reagents for analysis of urine, 408 
Receptacles for urine, 22 
Records of urinary examinations, 

402 
Red blood-corpuscles, 232 
Relapsing fever, urine in, 384 
Relative solids of the urine, 37 
Removal of albumin by heat, 131 
Renal calculus, 326 

casts, 249 

colic, 327, 342, 344 

embolism, 329 

epithelivim, 244 
Retention of urine, 25 
Rheumatism, acute articular, urine in, 

397 

Saccharimeter, Einhorn's, 162 
Salkowski-Ludwig method for esti- 
mating uric acid, 67 



INDEX. 



417 



Santonin in the urine, 29 
Sarcina urinfe, 267 
Sarcolactic acid in the urine, 98 
Scarlet fever, urine in, 390 
Scurvy, urine in, 399 
Sediment-glass, 206 
Sediments, ammonio-magnesium phos- 
phate in, 217 

ammonium-urate in, 213 

amorphous urates in, 214 

bilirubin in, 226 

blood in, 232 

calcium oxalate in, 219 
phosphate in, 218 

classihcatiotr of, 209 

cystin in, 223 

epithelium in, 24.3 

extraneous substances in, 263 

fragments of tumors in, 35 1 

hematoidin in, 226 

hippuric acid in, 81 

leucin in, 226 

leucocytes in, 238 

mounting of, 264 

non-organized, 2lo 

organized, 232 

preparation of, for microscopic 
examination, 208 

pus in, 238 

renal casts in, 249 

spermatozoa in, 260 

tyrosin in, 228 

urates in, 212 

uric acid in, 210 
Seminal cells, 247 
Senile interstitial nephritis, 313 
Serum-albumin, 120 
Serum-globulin, 135 
Sherer's test for leucin, 227 
Silver nitrate, standard solution of, 

103 
Skatoxyl-potassium sulphate, 88 

clinical significance of, 89 
Smallpox, urine in, 392 
Smegma bacilli in the urine, 326 
Smoky color of the urine, 27 
Soda, chlorinated, solution of, 51 
Sodium chloride, 100 

hypobromite solution of, 52 

nitrite, 186. See Ehrlich'' s Reac- 
tion. 

urate, 212 
Solids of the urine, 37 

by specific gravity, 40 

determination of, 39 

relative and absolute, 37 
Specific gravity, 34 

causes of variation, 34 
method of taking, 37 



Spermatozoa in the urine, 260 

detection of, 261 
Squibb' s apparatus for urea, 50 
Staining of tubercle bacilli, 325 

of gonococci, 268 
Standard solution of barium chloride, 
114 

of nitrate of silver, 103 

of uranium nitrate, no 
Subacute glomerular nephritis, 302 
Succinic acid in the urine, 98 
Sugar in the urine, 147 

detection of, 148 

methylene-blue test for, 156 

quantitative determination of, 1 57 
Sulphanilic acid, 186. See Ehrlicli' s 

Reaction. 
Sulphates in the urine, 112 

clinical significance of, 113 

detection of, 113 

ethereal, 84 

quantitative determination of, 

"3, 115 

Sulphuretted hydrogen in the urine, 

31 



Tabular arrangement of Heller's 

tests, 404 
Taenia echinococcus, 271 
Tauret's test for albumins, 130 
Teichmann's test for blood pigment, 

237 

crystals, 238 
Temporary glycosuria, 370, 374 
Tests, chemical, order of application 

of, 405 

for albumin, 124, 127 
Total solids, 38 
Toxicity of the urine, 198 
Transparency of the urine, 29 
Traumatic glycosuria, 371 
Tribromphenol, 90 
Triple phosphate, crystals of, 217 
Trommer's test for sugar, 149 
Trypsin in the urine, 99 
Tubercle bacilli in the urine, detec- 
tion of, 325 
Tuberculosis, local caseating, 323 

of the bladder, 348 

of the kidneys, 323 

of the prostate, 358 

pulmonary, urine in, 386 
Tumors of the bladder, 350 

of the kidney, 330 
Turbidity due to amorphous urrltes, 30 

due to bacteria, 30 

due to earthy phosphates, 29 
Typhoid bacillus in the urine, 268, 383 



418 



INDEX. 



Typhoid fever, urine in, 382 
Typhus fever, urine in, 384 
Tyrosin, 228 

clinical significance of, 230 

detection of, 228 



Uhle, table of, 44 

Uranium nitrate, standard solution of, 

no 
Urates, 212 
Urea, detection of, 47 

ferment, ^^ 

oxalate, 41 

phosphate, 41 
Urea, properties of, 41 

quantitative determination of, 47 

theory of formation of, 43 
Uremia, 367 
Ureometer, Doremus' , 56 

Hinds', 57 
Ureteral ephhelium, 246 
Ureteritis, 343 
Urethral epithelium, 247 
Urethritis, 359 
Uric Acid, 59 

clinical significance of, 66, 215 
crystals of, 210 
decomposition products of, 61 
detection of, 66 

quantitative determination of, 67 
properties of, 62 
Urinary coloring-matters, 91 . 

concretions, 272 

chemic examination of, 282 
composition of, 274 

constituents, Parkes' table of, 21 

cryoscopy, 1 18 

sediments, 201 

method of obtaining, 202 
Urine, abnormal constituents of, II9 

alkalinity of, 32 

ammoniacal decomposition of. 33 

analvsis of, apparatus for, 408 

black, 28 

color of, 25 

glass, 206 

increased acidity of, 34 
quantity of, 24 

inorganic constituents of, lOO 

normal, 21 

odor of, 30 

of chronic disease, 381 

organic constituents of, 41 

preservatives for, 23 

reaction of, 31 

reagents for analysis of, 408 

receptacles for, 22 

relative solids of, 37 



Urine, retention of, 25 

solids of, ^J 

specific gravity of, 34 

toxicity of, 198 

transparency of, 29 

turbidity of, 29 

typhoid bacilli in, 268, 383 
Urinometer, 35 

glass, 35 
Urinous odor, 30 
Urobilin, clinical significance of, 93 

detection of, 93 

normal, 91 

origin of, 91 

pathologic, 91 
Urochrome, 93 

detection of, 94 
Uroerythrin, 95 

detection of, 96 

significance of, 95 
Urophaein test, 93 
Urorosein, 96 

detection of, 96 
Urostealith calculi, 281 



Vaginal discharge in the urine, 243, 
248 
epithelium, 248 

Vegetable substances in the urine, 28 

Vesical calculus, 346 

Villous tumor of the bladder, 350 

Vogel's scale of colors, 26 

Volatile acids, 30 

Volhard and Falck's method of esti- 
mating chlorine, 105 



Waxy casts, 253 

Weidel's reaction for heteroxanthin, 

for paraxanthin, 76 
Weyl's test for kreatinin, 80 



Xanthin, 73 

bases, 72 

isolation of, 76 

concretions, 280 

detection of, 74 
Xanthoproteic reaction, 1 19 



Veast fungus in the urine, 266 
Yellow atrophy of the liver, acute, 

394 
fever, urine in, 383 
Yvon and Berlioz, comparative table 
of, 22 



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StelwagonV 
Diseases of the Skin 



A Treatise on Diseases of the Skin. For Advanced Students and 
Practitioners. By Henry W. Stelwagon, M. D., Ph.D., Clinical Pro- 
fessor of Dermatology, Jefferson Medical College and Woman's Medical 
College, Philadelphia ; Dermatologist to the Howard and to the Phila- 
delphia Hospitals. Handsome octavo of 1115 pages, with 220 text- 
cuts and 26 full-page colored hthographic and half-tone plates. Cloth, 
$6.00 net ; Sheep or Half Morocco, ^7.00 net. 

COMBINING A THOROUGH TREATISE WITH A COMPLETE ATLAS 
SECOND EDITION — FIRST EDITION EXHAUSTED IN SIX MONTHS 

The exhaustion of the first edition of this work in a period of six months, and 
the many comphmentary review notices have been exceedmgly gratifying. Such 
a kind reception permits the inference that the predominant aim kept in view in 
its preparation, of giving the general physician a treatise written on plain and 
practical lines, with abundant helpful case-illustrations, has been successful. 
While the short time that has elapsed since its appearance makes a revision 
unnecessary, the author has taken advantage of this opportunity to correct some 
typographical errors, and to change a few expressions that seemed of somewhat 
ambiguous meaning. 

PERSONAL AND PRESS OPINIONS 



John T. Bowen, M.D., 

Professor of Dermatology, Harvard University Medical School, Bostofi. 

" It gives me great pleasure to endorse Dr. Stelwagon 's book. The clearness of description 
is a marked feature. It is also very carefully compiled. It is one of the best text-books yet 
published and a credit to American dermatology." 

Grover W. Wende, M.D., 

Clinical Professor of Dermatology, University of Buffalo. 

" I have recommended that the work be included in the catalogue of the University of 
Buffalo. I think you are to be congratulated on bringing out one of the very best v/orks 
published in the English language." 

Boston Medical and Surgical Journal 

" We can cordially recommend Dr. Stelwagon's book to the profession as the best text- 
book on dermatology, for the advanced student and general practitioner, that has been brought 
strictly up to date. . . . The photographic illustrations are numerous, and many of them are 
of great excellence." 



DISEASES OF THE EYE, 



DeSchweinitz's 
Diseases of the Eye 

Fourth Edition, Revised, Enlarged, and Entirely Reset 



Diseases of the Eye : A Handbook of Ophthalmic Practice. 
By G. E. DeSchweinitz, M.D., Professor of Ophthalmology in the Uni- 
versity of Pennsylvania, Philadelphia, etc. Handsome octavo of 773 
pages, 280 text-illustrations, and 6 chromo-lithographic plates. Cloth, 
S5.00 net ; Sheep or Half Morocco, ^6.00 net. 

WITH 280 TEXT-ILLUSTRATIONS AND 6 COLORED PLATES 

In this new edition the text has been thoroughly revised, and the entire work 
has been reset. Many new chapters have been added, such as Thomson's Lantern 
Test for Color-Bhndness ; Hysteric Alopecia of the Eyelids ; Metastatic Gonor- 
rheal Conjunctivitis ; Grill-hke Keratitis (Haab); the so-called Holes in the Macula ; 
Divergence-paralysis ; Convergence-paralysis, and many others. A large number 
of therapeutic agents comparatively recently introduced, particularly the newer 
silver salts, are given in connection with the diseases in which they are indicated. 
The illustrative feature of the work has been greatly enhanced in value by the 
addition of many new cuts and six full-page chromo-lithographic plates, all most 
accurately portraying the pathologic conditions which they represento 



PERSONAL AND PRESS OPINIONS 



Samuel Theobald, M.D., 

Clinical Professor of Ophthalmology, Johns Hopkins University, Baltimore. 
" It is a work that I have held in high esteem, and is one of the two or three books upon 
the eye which I have been in the habit of recommending to my students in the Johns Hopkins 
Medical School." 

Late William Pepper, M.D., 

Professor of Theory and Practice of Medicine and Clinical Medicine, Utiiversity of Penn- 
sylvania. 
"A work that will meet the requirements not only of the specialist, but also of the general 
practitioner in a rare degree. I am satisfied that unusual success awaits it." 

British Medical Journal 

" A clearly written, comprehensive manual. One which we can commend to students as a 
reliable text-book, written with an evident knowledge of the wants of those entering upon the 
study of this special branch of medical science." 



SAUNDERS' BOOKS ON 



Barton and Welly-' 
Medical Thesaurus 

A NEW WORK— JUST ISSUED 



A Thesaurus of Medical Words and Phrases. By Wilfred M. 
Barton, A. M., Assistant to Professor of Materia Medica and Thera- 
peutics, and Lecturer on Pharmacy, Georgetown University, Washing- 
ton, D. C. ; and Walter A. Wells, M. D., Demonstrator of Laryn- 
gology and Rhinology, Georgetown University, Washington, D. C. 
Handsome octavo of about 650 pages. Cloth, ^0,00 net; Sheep or 
Half Morocco, $o.QO net. 

THE ONLY MEDICAL THESAURUS EVER PUBLISHED 

This work is the only Medical Thesaurus ever published. It aims to perform 
for medical literature the same services which Roget'swork has done for literature 
in general ; that is, instead of, as an ordinary dictionary does, supplying the 
meaning to given words, it reverses the process, and when the meaning or idea 
is in the mind, it endeavors to supply the fitting term or phrase to express that 
idea. To obviate constant reference to a lexicon to discover the meaning of 
terms, brief definitions are given before each word. As a dictionary is of service 
to those who need assistance in interpreting the expressed thought of others, the 
Thesaurus is intended to assist those who have to write or to speak to give proper 
expression to their own thoughts. In order to enhance the practical application 
of the book cross references from one caption to another have been introduced, 
and terms inserted under more than one caption when the nature of the term 
permitted. In the matter of synonyms of technical words the authors have per- 
formed for medical science a service never before attempted. Writers and 
speakers desiring to avoid unpleasant repetition of words will find this feature 
of the work of invaluable service. Indeed, this Thesaurus of medical terms and 
phrases will be found of inestimable value to all persons who are called upon 
to state or explain any subject in the technical language of medicine. To this 
class belong not only teachers in medical colleges and authors of medical books, 
but also every member of the profession who at some time may be required to 
deliver an address, state his experience before a medical society, contribute to 
the medical press, or give testimony before a court as an expert witness. 



EYE. EAR, NOSE, AND THROAT. 



American Text-Book qf 
Eye, Ear, Nose, and Throat 



American Text=Book of Diseases of the Eye, Ear, Nose, and 
Throat. Edited by G. E. de Schweinitz, M.D., Professor of Ophthal- 
mology in the University of Pennsylvania ; and B. Alexander Randall, 
I\I. D., Clinical Professor of Diseases of the Ear in the University of 
Pennsylvania. Imperial octavo, 125 i pages, with 766 illustrations, 59 
of them in colors. Cloth, $7.00 net ; Sheep or Half Morocco, $8.00 net. 

This work is essentially a text-book on the one hand, and, on the other, a 
volume of reference to which the practitioner may turn and find a series of articles 
written by representative authorities on the subjects portrayed by them. There- 
fore, the practical side of the question has been brought into prominence. Par- 
ticular emphasis has been laid on the most approved methods of treatment. 

American Journal of the Medical Sciences 

" The different articles are complete, forceful, and, if one may be permitted to use the term, 
'snappy.' in decided contrast to some of the labored but not more learned descriptions which 
have appeared in the larger systems of ophthalmology." 

Hyde and Montgomery's 
Syphilis and Venereal 

Syphilis and the Venereal Diseases. By James Nevins Hyde, 

M. D., Professor of Skin, Genito-Urinary, and Venereal Diseases, and 
Frank H. Montgomery, M. D., Associate Professor of Skin, Genito- 
Urinary, and Venereal Diseases in Rush Medical College, in Affiliation 
with the University of Chicago, Chicago. Octavo volume of 594 pages, 
profusely illustrated. Cloth, ^4.00 net. 

SECOND EDITION, REVISED AND GREATLY ENLARGED 

In this edition every page has received careful revision ; many subjects, 
notably that on Gonorrhea, have been practically rewritten, and much new mate- 
rial has been added. A number of new cuts have also been introduced, besides 
a series of beautiful colored lithographic plates. 

American Journal of Cutaneous and Genito-Urinary Diseases 

" It is a plain, practical, and up-to-date manual containing just the kind of information 
that physicians need to cope successfully with a troublesome class of diseases." 



SAUNDERS' BOOKS ON 



THE BEST l\l11 eric Sin STANDARD 

Illustrated Dictionary 

Third Revised Edition — Just Issued 



The American Illustrated Medical Dictionary. A new and com- 
plete dictionary of the terms used in Medicine, Surgery, Dentistry, 
Pharmacy, Chemistry, and kindred branches ; with over lOO new and 
elaborate tables and many handsome illustrations. By W. A. Newman 
Borland, M. D., Editor of '' The American Pocket Medical Diction- 
ary." Large octavo, nearly 8oo pages, bound in full flexible leather. 
Price, $4.50 net; with thumb index, ^5.00 net. 

THIRD EDITION IN THREE YEARS— 12,500 COPIES 

In this edition the book has been subjected to a thorough revision. The 
author has also added upward of one hundred important new terms that have 
appeared in medical literature during the past few months. 

Howard A. Kelly. M. D., 

Professor of Gynecology, Johns Hopkins University, Baltitnore. 

" Dr. Dorland's Dictionary is admirable. It is so well gotten up and of such convenient 
size. No errors have been found in my use of it." 

American Year-Book 



Saunders' American Year=Book of Medicine and Surgery. A 

Yearly Digest of Scientific Progress and Authoritative Opinion in all 
Branches of Medicine and Surgery, drawn from journals, monographs, 
and text-books of the leading American and foreign authors and inves- 
tigators. Arranged, with critical editorial comments, by eminent 
American specialists, under the editorial charge of George M. Gould, 
A. M., M. D. In two volumes : Vol. I. — General Mediciiie, octavo, 715 
pages, illustrated; Vol. II. — General Surgery, octavo, 684 pages, illus- 
trated. Per vol. : Cloth, $3.00 net ; Half Morocco, $l.J^ net. Sold 
by Subscription. 

In these volumes the reader obtains not only a yearly digest, but also the 
invaluable annotations and criticisms of the editors. As usual, this issue of the 
Year-Book is amply illustrated. 

The Lancet, London 

" It is much more than a mere compilation of abstracts, for, as each section is entrusted to 
experienced and able contributors, the reader has the advantage of certain critical commen- 
taries and expositions . . . proceeding from writers fully qualified to perform these tasks." 



AOSE, THROAT, AND EAR. 



Cradle's 
Nose, Pharynx, and Ear 

Diseases of the Nose, Pharynx, and Ear. By Henry Gradle, 
M. D., Professor of Ophthalmology and Otology, Northwestern Uni- 
versity Medical School, Chicago. Handsome octavo of 547 pages, 
illustrated, including two full-page plates in colors. Cloth, 1^3.50 net. 

INCLUDING TOPOGRAPHIC ANATOMY 

This volume presents diseases of the Nose, Pharynx, and Ear as the author 
has seen them during an experience of nearly twenty-five years. In it are 
answered in detail those questions regarding the course and outcome of diseases 
which cause the less experienced observer the most anxiety in an individual case. 
Topographic anatomy has been accorded liberal space. 

Pennsylvania Medical Journal 

"This is the most practical volume on the nose, pharynx, and ear that has appeared 
recently. ... It is exactly what the less experienced observer needs, as it avoids the confusion 
incident to a categorical statement of everybody's opinion." 

Kyle's 
Diseases of Nose anb Throat 



Diseases of the Nose and Throat. By D. Braden Kyle, M. D., 
Clinical Professor of Laryngology and Rhinology, Jefferson Medical 
College, Philadelphia ; Consulting Laryngologist, Rhinologist, and 
Otologist, St. Agnes' Hospital. Octavo, 646 pages; over 150 illus- 
trations, and 6 lithographic plates in colors. Cloth, ;^4.oo net. 

THIRD REVISED EDITION— JUST ISSUED 

Three large editions of this excellent work have been called for in as many 
years. In this edition the author has revised the text thorous^hly, brinc^ing 
it absolutely down to date. With the practical purpose of the book in mind, ex- 
tended consideration has been given to treatment, each disease being considered in 
full, and definite courses being laid down to meet special conditions and symptoms. 

Dudley S. Reynolds, M. D., 

Formerly Professor of Ophthalmology and Otology, Hospital College of Medicine, Lor/isville. 
" It is an important addition to the text-books now in use, and is better adapted to the uses 
of the student than any other work with which I am familiar. I shall be pleased to commend 
Dr. Kyle's work as the best text-book." 



saujYders' books on 



Brtihl, Politzer, and Smith's 
Otology 



Atlas and Epitome of Otology. By Gustav Bruhl, M. D., of 

Berlin, with the collaboration of Professor Dr. A. Politzer, of 
Vienna. Edited, with additions, by S. MacCuex Smith, ]\I. D., Clin- 
ical Professor of Otology, Jefferson Medical College, Philadelphia. 
With 244 colored figures on 39 Hthographic plates, 99 text illustra- 
tions, and 292 pages of text. Cloth, S3. 00 net. In Saunders' Hand- 
Atlas Scries. 

INCLUDING ANATOMY AND PHYSIOLOGY 

The work is both didactic and clinical in its teaching. A special feature is 
the very complete exposition of the minute anatomy of the ear, a working knowl- 
edge of which is so essential to an intelligent conception of the science of otology. 
The association of Professor Politzer and the use of so many valuable specimens 
from his notably rich collection especially enhance the value of the treatise. The 
work contains everything of importance in the elementary study of otology. 

Clarence j. Blake, M. D., 

Professor of Otology in Harvard University Medical School, Bosto?t. 

" The most complete work of its kind as yet published, and one commending itself to both 
the student and the teacher in the character and scope of its illustrations." 

Grtinwald and Grayson's 
Diseases of the Larynx 

Atlas and Epitome of Diseases of the Larynx. By Dr. L 

Grunwald, of Munich. Edited, with additions, by Charles P. Gray- 
son, M. D., Physician-in-Charge, Throat and Xose Department, Hos- 
pital of the University of Pennsylvania. With 107 colored figures on 
44 plates, 25 text-illustrations, and 103 pages of text. Cloth, 32.50 
net. I71 Sannders' Hand-Atlas Series. 

In this work the author has given special attention to the chnical portion, the 
sections on diagnosis and treatment being particularly full. The plates portray, 
with a remarkable fidelity to nature, pathologic conditions that it would require 
a number of years to duplicate in practice. A knowledge of the histology of the 
morbid processes being essential to a proper understanding of them, twelve plates, 
showing the most important elementan.- alterations, have been included. 

British Medical Journal 

" Excels everything we have hitherto seen in the way of colored illustrations of diseases of 
the larynx. . . . Not only valuable for the teaching of laryngology, it will prove of the greatest 
help to those who are perfecting themselves by private study." 



DISEASES OF THE EYE. 



Haab and DeSchweinitz's 
External Diseases qf the Eye 



Atlas and Epitome of External Diseases of the Eye. By Dr. O. 

Haab, of Zurich. Edited, with additions, by G. E. deSchweinitz, 
M. D., Professor of Ophthalmology, University of Pennsylvania. With 
^6 colored illustrations on 40 lithographic plates and 228 pages of 
text. Cloth, $3.00 net. /;/ Saunders Hand-Atlas Scries. 

This new work of the distinguished Ziirich ophthalmologist is destined to 
become a valuable handbook in the library of every practising physician. The 
conditions attending diseases of the external eye, which are often so complicated, 
have probably never been more clearly and comprehensively expounded than in 
the forelying work, in which the pictorial most happily supplements the verbal 
description. The price of the book is remarkably low. 

The Medical Record, New York 

"The work is excellently suited to the student of ophthalmology and to the practising 
physician. It cannot fail to attain a well-deserved popularity." 

Haab and DeSchweinitz V 
Ophthalmoscopy 



Atlas and Epitome of Ophthalmoscopy and Ophthalmoscopic 
Diagnosis. By Dr. O. Haab, of Ziirich. From the TJiird Revised 
and Enlarged German Edition. Edited, with additions, by G. E. 
deSchweinitz, M. D., Professor of Ophthalmology, University of 
Pennsylvania. With 152 colored lithographic illustrations and 85 
pages of text. Cloth, ^3.00 net. In Saunders' Hand- Atlas Series. 

The great value of Prof. Haab's Atlas of Ophthalmoscopy and Ophthalmo- 
scopic Diagnosis has -been fully established and entirely justified an English 
translation. Not only is the student made acquainted with carefully prepared 
ophthalmoscopic drawings done into well-executed lithographs of the most im- 
portant fundus changes, but, in many instances, plates of the microscopic lesions 
are added. The whole furnishes a manual of the greatest possible service. 

The Lancet, London 

"We recommend it as a work that should be in the ophthalmic wards or in the library of 
every hospital into which ophthalmic cases are received." 



lo SAUNDERS' BOOKS ON 

American Text-Book of 

Genito-Urinary, Syphilis, Skin 

American Text=book of Genito=Urinary Diseases, Syphilis, and 
Diseases of the Skin. Edited by L. Boltox Bangs, M. D., late Prof, 
of Genito-Urinar}' Surgety, University and Bellevue Hospital Medical 
College, New York ; and W, A. Hardaway, M. D., Professor of Diseases 
of the Skin, Missouri Medical College. Imperial octavo, 1229 pages, 
with 300 engravings, 20 colored plates. Cloth, 37. 00 net ; Sheep or 
Half Morocco, $8.00 net. 

CONTAINING 20 COLORED PLATES 

This work is intended for both the student and practitioner, giving, as it does, 
a comprehensive and detailed presentation of the subjects discussed. The work 
is original and fully representative. The illustrations, many of which are in 
colors, portray the conditions with rare fidelity, and will be found invaluable as 
an aid in diagnosis. 

Journal of the Americein Medical Association 

" This voluminous work is thoroughly up-to-date, and the chapters on genito-urinary dis- 
eases are especially valuable. The illustrations are fine and are mostly original. The section 
on dermatology is concise and in every way admirable." 

SennV 

Genito-Urinary Tuberculosis 

Tuberculosis of the Qenito=Urinary Organs, Male and Female. 

By N. Senn, M.D., Ph.D., LL.D., Professor of Surgery in Rush Med- 
ical College; Attending Surgeon to the Presbyterian Hospital, Chicago. 
Octavo volume of 317 pages, illustrated. Cloth, 33.00 net. 

MALE AND FEMALE 

Tuberculosis of the male and female genito-urinary organs is such a frequent, 
distressing, and fatal affection that a special treatise on the subject appears to fill a 
gap in medical literature. In the present work the bacteriology of the subject has 
received due attention, the modern resources employed in the differential diagnosis 
between tubercular and other inflammatory affections are fully described, and the 
medical and surgical therapeutics are discussed in detail. 

British Medical Journal 

" The book will well repay perusal. It is the final word, as our knowledge stands, upon 
the diseases of which it treats, and will add to the reputation of its distinguished author." 



DISEASES OF THE SKIN. 



Mracek and Stelwagon's 
Diseases of the Skin 

Atlas and Epitome of Diseases of the Skin. By Prof. Dr. Franz 
Mracek, of Vienna. Edited, with additions, by Henry W. Stelwagon, 
M.D., Clinical Professor of Dermatology, Jefferson Medical College, 
Philadelphia. With 63 colored plates, 39 half-tone illustrations, and 
200 pages of text. Cloth, S3. 50 net. In Saunders'' Hand- Atlas Series. 

CONTAINING 63 COLORED PLATES 

This volume, the outcome of years of scientific and artistic work, contains, 
together with colored plates of unusual beauty, numerous illustrations in black, 
and a text comprehending the entire field of dermatology. The illustrations are 
all original and prepared from actual cases in Mracek' s clinic, and the execution 
of the plates is superior to that of any, even the most expensive, dermatologic 
atlas hitherto published. 

American Journal of the Medical Sciences 

" The advantages which we see in this book and which recommend it to our minds are: 
First, its handiness ; secondly, the plates, which are excellent as regards drawing, color, and the 
diagnostic points which they bring out." 

Mracek arti) Bangs' 
Syphilis and Venereal 

Atlas and Epitome of Syphilis and the Venereal Diseases. 

By Prof. Dr. Franz Mracek, of Vienna. Edited, with additions, by 
L. Bolton Bangs, M. D., late Prof, of Genito-Urinary Surgery, Univer- 
sity and Bellevue Hospital Medical College, New York. With 71 
colored plates and 122 pages of text. Cloth, ^3.50 net. In Saunders' 
Hand- Atlas Series. 

CONTAINING 71 COLORED PLATES 

According to the unanimous opinion of numerous authorities, to whom the 
original illustrations of this book were presented, they surpass in beauty anything 
of the kind that has been produced in this field, not only in Germany, but 
throughout the literature of the world. 

Robert L. Dickinson, M. D., 

Art Editor of " The Americaii Text-Book of Obstetrics." 
" The book that appeals instantly to me for the strikingly successful, valuable, and graphic 
character of its illustrations is the ' Atlas of Syphilis and the Venereal Diseases.' I know of 
nothing in this country that can compare with it." 



12 SAUXDERS' BOOKS ON 

Grant's 
Face, Mouth, and Jaws 

A Text=Book of the Surgical Principles and Surgical Diseases of 
the Face, Mouth, and Jaws. For Dental Students. By H. Horace 
Grant, A. AL, ]\I. D., Professor of Surgery and of Clinical Surgery, 
Hospital College of Aledicine ; Professor of Oral Surgery-, Louisville 
College of Dentistry, Louisville. Octavo volume of 231 pages, with 
68 illustrations. Cloth, S2. 50 net. 

FOR DENTAL STUDENTS 

This text-book, designed for the student of dentistr\', succinctly explains the 
principles of dental surgery apphcable to all operative procedures, and also dis- 
cusses such surgical lesions as are likely to require diagnosis and perhaps treat- 
ment by the dentist. The arrangement and subject-matter cover the needs of the 
dental student without encumbering him with any details foreign to the course of 
instruction usually followed in dental colleges at the present time. The work 
includes, moreover, such emergency procedures as not alone the dentist and 
physician, but also the layman, may be called upon to perform. These, like the 
other subjects in the book, have been described in clear, concise language. 

Grtinwald and Newcomb's 
Mouth, Pharynx, and Nose 

Atlas and Epitome of Diseases of tlie Mouth, Pharynx, and 
Nose. By Dr. L. Gruxwald, of ^Munich. From the Second Revised 
and Enlarged German Edition. Edited, with additions, by James E. 
Newcomb, M. D., Instructor in Laryngology^ Cornell University Medical 
School. With 102 illustrations on 42 colored lithographic plates, 41 
text-cuts, and 219 pages of text. Cloth, 33.00 net. In Saunders' 
Hand- Atlas Series. 

INCLUDING ANATOMY AND PHYSIOLOGY 

In designing this atlas the needs of both student and practitioner were kept 
constantly in mind, and as far as possible typical cases of the various diseases 
were selected. The illustrations are described in the text in exactly the same way 
as a practised examiner would demonstrate the objective findings to his class, the 
book thus serving as a substitute for actual clinical work. The illustrations them- 
selves are numerous and exceedingly well executed, portraying the conditions so 
strikingly that their study is almost equal to examination of the actual specimens. 
The editor has incorporated his own valuable experience, and has also included 
extensive notes on the use of the active principle of the suprarenal bodies in the 
materia medica of rhinology and laryngology. 



EYE, EAR, NOSE, AND THROAT. 13 



Jackson on the Eye 



A Manual of the Diagnosis and Treatment of Diseases of the Eye. 

By Edward Jackson, A. M., M. D., Emeritus Professor of Diseases of 
the Eye in the Philadelphia Polyclinic. i2mo volume of 535 pages, 
with 178 beautiful illustrations, mostly from drawings by the author. 

Cloth, 32.50 net. 

In this book more attention is given to the conditions that must be met and 
dealt with early in ophthalmic practice than to the rarer diseases and more difficult 
operations that may come later. It is designed to furnish efficient aid in the actual 
work of dealing with disease, and therefore gives the place of first importance to 
the conditions present in actual clinical work. A special chapter is devoted to the 
relations of ocular symptoms and lesions to general diseases. 

The Medical Record, New York 

" It is truly an admirable work. . . . Written in a clear, concise manner, it bears evidence 
of the author's comprehensive grasp of the subject. The term ' multum in parvo ' is an appro- 
priate one to apply to this work. It will prove of value to all who are interested in this branch 
of medicine." 

Friedrich and Curtis' 
Nose, Larynx, and Ear 



Rhinology, Laryngology, and Otology, and Their Significance in 
General Medicine. By Dr. E. P. Friedrich, of Leipzig. Edited by 
H. HoLBROOK Curtis, M. D., Consulting Surgeon to the New York Nose 
and Throat Hospital. Octavo volume of 350 pages. Cloth, ;^2.50 net. 

INCLUDING THEIR SIGNIFICANCE IN GENERAL MEDICINE 

In this work the author's object has been to point out the interdependence 
between disease of the entire organism and diseases of the nose, pharynx, larynx, 
and ear, and to incorporate the new discoveries of these specialties into the scheme 
of general medicine. The author has endeavored to bring to the attention of the 
general practitioner special symptoms and methods of the greatest importance to 
him. 

Boston Medical and Surg(ical Journal 

" Tliis task he has performed admirably, and has given both to the general practitioner and 
to the specialist a book for collateral reference which is modern, clear, and complete." 



14 SAUNDERS' BOOKS ON 

Os(den on the Urine 



Clinical Examination of Urine and Urinary Diagnosis. A Clinical 
Guide for the Use of Practitioners and Students of Medicine and Sur- 
gery. By J. Bergen Ogden, M. D., Late Instructor in Chemistry, 
Harvard University Medical School ; Formerly Assistant in Clinical 
Pathology, Boston City Hospital. Octavo, 425 pages, 54 illustrations, 
and a number of colored plates. Cloth, ;^3.oo net. 

A CLINICAL GUIDE FOR PRACTITIONER AND STUDENT 

This work presents in as concise a manner as possible the chemistry of the 
urine and its relation to physiologic processes ; the most approved working methods, 
both qualitative and quantitative ; the diagnosis of diseases and disturbances of the 
kidneys and urinary passages. Special attention has been paid to diagnosis by 
the character of the urine, the diagnosis of diseases of the kidneys and urinary 
passages ; an enumeration of the prominent clinical symptoms of each disease ; 
and the peculiarities of the urine in certain general diseases. 

The Lancet, London 

" We consider this manual to have been well compiled ; and the author's own experience^ 
so clearly stated, renders the volume a useful one both for study and reference." 



Vecki's Sexual Impotence 



The Pathology and Treatment of Sexual Impotence. By Victor 
G. Vecki, M. D. From the Second Revised and Enlarged German. 
Edition. i2mo volume of 329 pages. Cloth, ;$2.oo net. 

THIRD EDITION, REVISED AND ENLARGED 

The subject of impotence has but seldom been treated in this country in the 
truly scientific spirit that its pre-eminent importance deserves, and this volume will 
come to many as a revelation of the possibilities of therapeutics in this important 
field. The reading part of the English-speaking medical profession has passed 
judgment on this monograph. The whole subject of sexual impotence and its 
treatment is discussed by the author in an exhaustive and thoroughly scientific 
manner. In this edition the book has been thoroughly revised, and new matter 
has been added, especially to the portion dealing with treatment. 

Johns Hopkins Hospital Bulletin 

" A scientific treatise upon an important and much neglected subject. . . . The treatment 
of impotence in general and of sexual neurasthenia is discriminating and judicious." 



CHEMISTRY, SKIN, AND VENEREAL DISEASES. 15 

American Pocket Dictionary Fourth Edition. Revised 

The x-\merican Pocket Medical Dictionary. Edited by W. A. 
Newman Borland, M. D., Assistant Obstetrician to the Hospital 
of the University of Pennsylvania. Containing the pronunciation 
and definition of the principal words used in medicine and kindred 
sciences. Flexible leather, with gold edges, ;^i.oo net ; with thumb 
index, $1.25 net. 
James W. Holland, M. D.. 

Professor of Medical Chemistry and Toxicology, and Dean, Jefferson Medical College, 
Philadelphia, 

" I am struck at once with admiration at the compact size and attractive exterior. I 
can recommend it to our students without reserve." 

Stelwagon's Essentials of Skin Fifth Revised Edition 

Essentials of Diseases of the Skin. By Henry W. Stel- 
WAGON, M. D., Ph.D., Clinical Professor of Dermatology in Jeffer- 
son Medical College and Women's Medical College, Philadelphia. 
Post-octavo of 276 pages, with 72 text-illustrations and 8 plates. 
Cloth, ;$i.oo net. In Saunders' QuestioJt-Compend Series. 
The Medical News 

" In line with our present knowledge of diseases of the skin. . . . Continues to main- 
tain the high standard of excellence for which these question compends have been noted." 

Wolffs Medical Chemistry Fifth Edition, Revised 

Essentials of Medical Chemistry, Organic and Inorganic. 
Containing also Questions on Medical Physics, Chemical Physiol- 
ogy, Analytical Processes, Urinalysis, and Toxicology. By Law- 
rence Wolff, M. D., Late Demonstrator of Chemistry, Jefferson 
Medical College. Revised by Smith Ely Jelliffe, M. D., Ph.D., 
Professor of Pharmacognosy, College of Pharmacy of the City of 
New York. Post-octavo of 222 pages. Cloth, ^i.oo net. In 
Saunders' Question- Conipend Series. 
New York Medical Journal 

" The author's careful and well-studied selection of the necessary requirements of the 
student has enabled him to furnish a valuable aid to the student." 

Martin's Minor Surgery, Bandaging, and the Venereal 

Diseases second Edition, Revised 

Essentials of Minor Surgery, Bandaging, and Venereal 
Diseases. By Edward Martin, A. M., M. D., Professor of Clin- 
ical Surgery, University of Pennsylvania, etc. Post-octavo, 166 
pages, with 78 illustrations. Cloth, ;^i.oo net. /;/ Saunders' 
Quesiion-Compend Series. 
The Medical News 

"The best condensation of the subjects of which it treats yet placed before the pro- 
fession." 

Jelliffe and Diekman's Chemistry 

A Text-Book of Chemistry. By Smith Ely Jelliffe, M. D., 
Ph.D., Professor of Pharmacology, and George C. Diekman, Ph.G., 
M. D., Professor of Theoretical and Applied Pharmacy, College of 
Pharmacy of the City of New York. Octavo, 550 pages, illustrated. 
In Preparation. 



i6 URINE, EYE, EAR, NOSE, AND THROAT. 

Wolfs Examination of Urine 

A Laboratory Handbook of Physiologic Chemistry and 
Urine-examination. By Charles G. L. Wolf, M. D., Instructor in 
Physiologic Chemistry, Cornell University Medical College, New 
York. 1 2mo volume of 204 pages, fully illustrated. Cloth, $1.25 net. 
British Medical Journal 

" The methods of examining the urine are very fully described, and there are at the 
end of the book some extensive tables drawn up to assist in urinary diagnosis." • 

Jackson's Essentials of Eye Third Revised Edition 

Essentials of Refraction and of Diseases of the Eye. By 
Edward Jackson, A. M., M. D., Emeritus Professor of Diseases of 
the Eye, Philadelphia PolycHnic. Post-octavo of 261 pages, 82 illus- 
trations. Cloth, 31.00 net. In Smindcrs Qiiestion-Compend Series. 
Johns Hopkins Hospital Bulletin 

'■ The entire ground is covered, and the points that most need careful elucidation 
are made clear and easy." 

Gleason's Nose and Throat Third Edition, Revised 

Essentials of Diseases of the Nose and Throat. By E. B. 
Gleason, S. B., M. D., CHnical Professor of Otology, Medico- 
Chirurgical College, Philadelphia, etc. Post-octavo, 241 pages, 1 12 
illustrations. Cloth, ^i.oo net. In Saunders Question Conipends^ 
The Lancet, London 

" The careful description which is given of the various procedures would be sufficient 
to enable most people of average intelligence and of slight anatomical knowledge to 
make a very good attempt at laryngoscopy." 

Gleason's Diseases of the Ear Third Edition, Revised 

Essentials of Diseases of the Ear. By E. B. Gleason, S. B., 
M. D., CHnical Professor of Otology, Medico-Chirurgical College, 
Phila., etc. Post-octavo volume of 214 pages, with 114 illustra- 
tions. Cloth, ;^ 1. 00 net. In Saunders Qnestion-Compend Series. 
Bristol Medico-Chirurgical Journal 

"We know of no other small work on ear diseases to compare with this, either in 
freshness of style or completeness of information." 

Wolffs Essentials of the Urine 

Essentials of Examination of Urine, Chemical and Micro- 
scopic, FOR Clinical Purposes. By Lawrence Wolff, M. D., 
Late Demonstrator of Chemistry, Jefferson Medical College, Phila- 
delphia. Post-octavo, 66 pages, illustrated. Cloth, 75 cents net. 
In Sannders' Question Conipends. 

Brockway's Medical Physics second Edition. Revised 

Essentials of Medical Physics. By Fred. J. Brockway, 
M. D., Late Assistant Demonstrator of Anatomy, College of Physi- 
cians and Surgeons, New York. Post-octavo, 330 pages ; 155 fine 
illustrations. Cloth, $1.00 net. /;/ Sanyiders' Question Compends. 
Medical Record, New York 

" It contains all that one need know on the subject, is well written, and is copiously 
illusi^rated." 



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